Affinage

POMC

Pro-opiomelanocortin · UniProt P01189

Round 2 corrected
Length
267 aa
Mass
29.4 kDa
Annotated
2026-04-28
130 papers in source corpus 52 papers cited in narrative 52 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

POMC encodes a polyprotein precursor that is proteolytically processed at dibasic cleavage sites by prohormone convertases in a tissue-specific manner to yield melanocortin peptides (ACTH, α-MSH, β-MSH, γ-MSH) and β-endorphin, which act through a family of five G-protein-coupled melanocortin receptors (MC1R–MC5R) to regulate adrenal steroidogenesis, skin/hair pigmentation, energy homeostasis, and nociception (PMID:6254047, PMID:1325670, PMID:8392067). In hypothalamic arcuate nucleus POMC neurons, leptin–STAT3, insulin–IR/TCPTP, serotonin–TrpC5, and apelin–APJ/Gβγ/KCNQ signaling pathways converge on neuronal excitability and α-MSH release, which activates MC4R on downstream PVH and MeA neurons to suppress feeding and modulate hepatic glucose production (PMID:12697721, PMID:28099839, PMID:30230471, PMID:27869800, PMID:33250721). POMC transcription is driven by Tpit/Pitx1 in the pituitary and by E2F1/DP1 in ectopic tumors, stimulated by CRF and LXRα, and repressed by glucocorticoids via an nGRE, by FoxO1 sequestration of STAT3, by NF-κB p50 binding, and by promoter DNA methylation modulated by MeCP2 (PMID:2698828, PMID:27935805, PMID:19036902, PMID:25510553, PMID:24078059, PMID:33462216). Loss-of-function POMC mutations in humans cause early-onset obesity, adrenal insufficiency, and red hair pigmentation, confirming POMC as a monogenic determinant of energy balance, adrenal function, and pigmentation (PMID:9620771).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1980 High

    Sequencing the human POMC gene revealed a single-gene precursor architecture with dibasic residue cleavage sites demarcating ACTH and β-lipotropin segments, establishing the structural basis for tissue-specific proteolytic processing into multiple bioactive peptides.

    Evidence Genomic DNA sequencing with heteroduplex analysis and comparison to bovine cDNA

    PMID:6254047

    Open questions at the time
    • Processing enzymes not yet identified
    • Tissue-specific processing rules not defined
  2. 1983 High

    CRF was identified as a physiological stimulus of POMC-derived peptide secretion from anterior pituitary via adenylate cyclase, while dopamine inhibits intermediate lobe output, defining the hormonal inputs controlling POMC product release at the pituitary level.

    Evidence Primary culture of rat anterior and intermediate pituitary cells with cAMP assay and in vivo peptide measurements

    PMID:6310240

    Open questions at the time
    • Intracellular signaling cascade from CRF to POMC transcription not mapped
    • Relative contribution of cAMP vs. other second messengers unclear
  3. 1986 Medium

    Central administration of ACTH and α-MSH suppressed feeding and antagonized κ-opioid-stimulated intake, establishing the concept of opposing melanocortin–opioid systems in energy homeostasis before melanocortin receptors were cloned.

    Evidence Intracerebroventricular injection of melanocortin peptides in rats with behavioral food-intake measurement

    PMID:3025825

    Open questions at the time
    • Receptor identity unknown at the time
    • Pharmacological approach cannot distinguish direct vs. indirect effects
  4. 1989 High

    Identification of a negative glucocorticoid response element (nGRE) in the proximal POMC promoter, where mutually exclusive binding of the glucocorticoid receptor and COUP-family factors determines glucocorticoid repression and cell-specific expression, established the first cis-regulatory logic for POMC transcription.

    Evidence Promoter deletion analysis in transgenic mice and cell culture with DNA-protein binding assays

    PMID:2698828

    Open questions at the time
    • Full set of transcription factors driving pituitary-specific expression not defined
    • Chromatin context of nGRE occupancy not addressed
  5. 1992 High

    Cloning of MC1R–MC5R defined the receptor family through which POMC-derived melanocortins signal, each coupling to adenylyl cyclase/cAMP, and revealed tissue-specific receptor expression explaining how a single precursor generates diverse physiological outputs.

    Evidence Molecular cloning with heterologous expression, binding assays, and cAMP signaling in transfected cells

    PMID:1325670 PMID:8185570 PMID:8392067 PMID:8463333

    Open questions at the time
    • Non-cAMP signaling pathways of MCRs incompletely characterized
    • Endogenous receptor stoichiometry and functional selectivity not addressed
  6. 1998 High

    Identification of compound heterozygous/homozygous POMC mutations in patients with early-onset obesity, adrenal insufficiency, and red hair provided the first human genetic proof that POMC is essential for energy homeostasis, adrenal function, and pigmentation.

    Evidence POMC gene sequencing in patients with defined multi-organ phenotype

    PMID:9620771

    Open questions at the time
    • Genotype-phenotype correlation across a range of POMC mutations incomplete
    • Relative contribution of individual POMC products to each phenotype unknown
  7. 2002 High

    Discovery that R236G disrupts a dibasic cleavage site to produce an aberrant β-MSH/β-endorphin fusion protein that binds MC4R but cannot activate it revealed that impaired POMC processing—not just absence of POMC—can cause obesity through generation of a dominant-negative-like melanocortin product.

    Evidence Metabolic labeling and receptor binding/cAMP assay with mutant POMC in transfected β-TC3 cells

    PMID:12165561

    Open questions at the time
    • Prevalence of processing-site mutations in broader obese populations unknown
    • Whether the fusion protein acts as a true competitive antagonist in vivo is unresolved
  8. 2003 High

    Leptin was shown to stimulate POMC transcription via STAT3, requiring Tyr1138 of the leptin receptor and a specific POMC promoter element, providing the molecular link between peripheral adiposity signals and hypothalamic melanocortin output.

    Evidence POMC promoter reporter assays, dominant-negative STAT3, ObRb mutant, and phospho-STAT3/POMC double immunohistochemistry in rat hypothalamus

    PMID:12697721

    Open questions at the time
    • Only ~37% of POMC neurons showed leptin-STAT3 activation; identity and regulation of the non-responding majority unclear
    • Other leptin-activated pathways in POMC neurons not dissected
  9. 2008 High

    N-terminal POMC mutations (C28F, L37F) were shown to redirect POMC from the regulated to the constitutive secretory pathway, preventing proper processing and causing obesity—establishing that signal-peptide-region integrity is required for POMC sorting to secretory granules.

    Evidence Metabolic labeling and Western blot of wild-type vs. mutant POMC secretion in β-TC3 cells

    PMID:18697863

    Open questions at the time
    • Sorting receptor or chaperone that recognizes the POMC N-terminus not identified
    • Whether constitutively secreted unprocessed POMC has any signaling activity is unknown
  10. 2014 High

    Epigenetic regulation of POMC was defined: MeCP2 prevents promoter DNA hypermethylation and cooperates with CREB1 to activate POMC transcription in hypothalamic neurons, while in pituitary, MeCP2 complexes with HDAC2/DNMT1 to repress POMC—revealing tissue-specific epigenetic gating of POMC expression.

    Evidence POMC-neuron-specific MeCP2 KO mice; bisulfite sequencing; luciferase assays with methylated promoter; co-IP of MeCP2/HDAC2/DNMT1 in pituitary cells

    PMID:24078059 PMID:24506071

    Open questions at the time
    • How MeCP2 switches between activator and repressor roles in different tissues is mechanistically unresolved
    • Contribution of other chromatin remodelers not assessed
  11. 2016 High

    α-MSH was shown to act as a postsynaptic neuromodulator at MC4R-expressing PVH neurons, potentiating glutamatergic satiety transmission from ARC to PVH, and a separate ARCPOMC→MeA projection was identified as an extrahypothalamic melanocortinergic satiety circuit.

    Evidence Optogenetics, chemogenetics, electrophysiology, and MC4R antagonist pharmacology in circuit-specific mouse models

    PMID:27869800 PMID:33250721

    Open questions at the time
    • Relative contribution of PVH vs. MeA projection to overall satiety unclear
    • Neuropeptide vs. fast neurotransmitter release from POMC neurons not fully dissected
  12. 2017 High

    Mitochondrial dynamics within POMC neurons emerged as a cell-intrinsic rheostat: TNFα-driven mitochondrial fusion increases POMC neuron excitability in obesity, while DRP1-mediated fission restrains leptin sensitivity and glucose sensing, with mTORC1 orchestrating functionally distinct GABAergic and glutamatergic POMC neuron subpopulations.

    Evidence Conditional KO of DRP1 and Raptor in POMC neurons; microglial TNFα and mitochondrial morphology imaging; electrophysiology; optogenetics and chemogenetics

    PMID:28190775 PMID:28489068 PMID:34644574

    Open questions at the time
    • How mitochondrial dynamics interface with POMC processing machinery is unknown
    • Whether mitochondrial fission/fusion directly affects α-MSH vesicle packaging is untested
  13. 2017 High

    Multiple ion channel and receptor mechanisms controlling POMC neuron excitability were defined: TrpC5 channels mediate leptin and serotonin 2C receptor-driven depolarization, while apelin acts via APJ/Gβγ/PLC-β to inhibit KCNQ M-type currents, establishing the electrophysiological integration point for diverse hormonal inputs.

    Evidence Conditional TrpC5 KO in POMC neurons with patch-clamp; pharmacological dissection of apelin signaling in POMC neurons with Gβγ inhibitor gallein and PLC/PKC inhibitors

    PMID:25782002 PMID:28099839

    Open questions at the time
    • Full ion channel repertoire of POMC neuron subpopulations not cataloged
    • Whether TrpC5 and KCNQ pathways converge in the same POMC neurons is unknown
  14. 2018 High

    The phosphatase TCPTP was identified as a fasting/feeding-regulated brake on insulin signaling in POMC neurons: elevated in fasting and obesity, TCPTP dephosphorylates the insulin receptor to silence insulin-responsive POMC neurons and their suppression of hepatic glucose production.

    Evidence POMC-neuron-specific TCPTP deletion with electrophysiology and hyperinsulinemic-euglycemic clamp studies

    PMID:30230471

    Open questions at the time
    • TCPTP targets beyond the insulin receptor in POMC neurons not mapped
    • How TCPTP is degraded upon feeding is mechanistically undefined
  15. 2021 High

    Intersectional genetic approaches revealed that POMCLepr+ and POMCGlp1r+ neuron subpopulations are largely nonoverlapping, with distinct electrophysiological properties and differential capacity to suppress feeding, establishing a functional microarchitecture within the POMC neuron population.

    Evidence Intersectional Cre/Dre mouse models with RiboTag translational profiling, electrophysiology, and chemogenetic feeding assays

    PMID:34002087

    Open questions at the time
    • Full molecular taxonomy of POMC neuron subtypes across brain regions incomplete
    • How subpopulation-specific outputs are integrated at downstream targets is undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include how POMC neuron subpopulation-specific neurotransmitter release (GABA vs. glutamate vs. α-MSH) is coordinately regulated, whether mitochondrial dynamics directly control POMC processing and peptide packaging, and the identity of sorting receptors that direct POMC to the regulated secretory pathway.
  • Sorting receptor for POMC into secretory granules not identified
  • Structural basis of POMC–prohormone convertase interaction unknown
  • Integration rules across POMC neuron subpopulations at downstream target neurons undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 8
Localization
GO:0005576 extracellular region 4 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-162582 Signal Transduction 10 R-HSA-112316 Neuronal System 6 R-HSA-1430728 Metabolism 4 R-HSA-392499 Metabolism of proteins 4 R-HSA-168256 Immune System 2
Partners
FOXO1MC1RMC3RMC4RMECP2PCSK2STAT3TRPC5

Evidence

Reading pass · 52 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1980 The human POMC genomic DNA encodes the corticotropin-β-lipotropin precursor as a single gene; nucleotide sequencing revealed pairs of basic amino acid residues (Lys-Arg) punctuating conserved segments corresponding to component peptide hormones ACTH and β-lipotropin, with no intervening sequence over the exon 3 region, establishing the structural basis for proteolytic processing. Genomic DNA isolation, electron microscope heteroduplex analysis, gel blotting, and nucleotide sequencing compared with bovine cDNA Proceedings of the National Academy of Sciences of the United States of America High 6254047
1983 The human POMC gene was chromosomally localized to 2p23 by in situ hybridization, establishing its genomic map position. In situ hybridization to stretched prometaphase chromosomes with high-resolution banding Proceedings of the National Academy of Sciences of the United States of America High 6196780
1983 CRF stimulates ACTH secretion from anterior pituitary cells and α-MSH secretion from pars intermedia cells via adenylate cyclase activation at the pituitary level; α1-adrenergic agents stimulate ACTH directly at the pituitary, while β-adrenergic and antidopaminergic agents act suprapituitarily. Dopamine receptor activation inhibits pars intermedia activity. Primary culture of rat anterior and intermediate pituitary cells; adenylate cyclase assay; in vivo peptide measurements Journal of steroid biochemistry High 6310240
1986 ACTH and α-MSH peptides in the rat anterior pituitary are differentially stored in distinct secretory granule populations within corticotropes, as revealed by double-label immunocytochemistry; three subtypes of corticotropes were distinguished by their relative content of ACTH vs. α-MSH immunoreactivity. Double-labeling immunocytochemistry (ferritin for α-MSH; colloidal gold for ACTH) at the electron microscopy level Cell and tissue research High 3004731
1986 ACTH-(1-24) and α-MSH administered intracerebroventricularly suppress spontaneous feeding and abolish the feeding-stimulatory effect of κ-opioid receptor agonists, establishing that melanocortin peptides play an inhibitory role in a melanocortin-opioid homeostatic system with opposing, mutually-balancing effects. Intracerebroventricular injection in adult rats; behavioral measurement of food intake Peptides Medium 3025825
1987 POMC-derived peptides (ACTH, β-endorphin, α-MSH) in brainstem baroreceptor areas of the rat originate from both hypothalamic arcuate nucleus neurons and local NTS neurons; surgical lesion and transection experiments defined two descending pathways (medial and lateral) through which hypothalamic POMC fibers innervate vasomotor centers. Radioimmunoassay of brainstem peptides; 10 types of surgical lesions/transections in rat; immunohistochemistry Brain research High 2829991
1988 POMC gene is expressed in many rat non-pituitary tissues (testis, duodenum, kidney, colon, liver, lung, stomach, spleen) producing a shorter (~800 nt) POMC-like mRNA compared with the ~1000 nt pituitary POMC mRNA, and the resulting peptides are processed differently or turned over faster in peripheral tissues. Northern blot hybridization with exon 3 riboprobe; gel filtration chromatography; radioimmunoassay of ACTH, β-endorphin, γ-MSH Endocrinology High 2836169
1989 Glucocorticoid repression of POMC transcription is mediated by a negative glucocorticoid response element (nGRE) in the proximal POMC promoter that also binds COUP-family transcription factors; mutually exclusive binding of the glucocorticoid receptor and COUP factors to the nGRE determines cell-specific expression and glucocorticoid repression. DNA-mediated gene transfer into transgenic mice and tissue culture cells; DNA-protein binding assays Genome High 2698828
1989 Peripheral γ-MSH peptides (derived from the N-terminal region of POMC) exert pressor, cardioaccelerator, and natriuretic effects dependent on central sympathetic drive and central vasopressinergic pathways; structure-activity studies identified the His-Phe-Arg-Trp core (γ-MSH-(5-8)/ACTH-(6-9)) as the minimal cardiovascular active sequence. Intravenous infusion with adrenergic/central lesion pharmacology in rats; structure-activity relationship with peptide fragments; intracarotid vs. intrajugular comparison The American journal of physiology Medium 2552843
1991 ACTH-(1-24) competes with dopamine D2 receptor agonist [3H]NPA binding in rat striatal membranes in an apparent competitive manner (increased Kd, unchanged Bmax), and structure-activity analysis showed chain length is a key determinant of this interaction; ACTH peptides also inhibit D2 antagonist binding in pituitary, septum, and substantia nigra. Radioligand binding assays with rat striatal membranes; Scatchard analysis; structure-activity with multiple ACTH fragments European journal of pharmacology Medium 1680721
1992 The murine and human melanocyte-stimulating hormone receptors (MC1R) and human ACTH receptor (MC2R) were cloned and identified as G-protein-coupled receptors; functional expression confirmed coupling to guanine nucleotide-binding proteins and defined the melanocortin receptor (MCR) subfamily. Molecular cloning, heterologous expression in cell lines, receptor binding assays Science (New York, N.Y.) High 1325670
1993 A fourth human melanocortin receptor (MC4R), expressed primarily in the brain (absent from adrenal cortex, melanocytes, and placenta), was cloned and shown to increase intracellular cAMP upon agonist stimulation; its pharmacological profile distinguishes it from previously described MCRs. Molecular cloning, Northern blot, in situ hybridization, transient and stable transfection in COS-1 and L-cells, cAMP assay, fluorescent in situ hybridization (chromosome 18q21.3) The Journal of biological chemistry High 8392067
1993 A third human melanocortin receptor (MC3R) was cloned; pharmacological characterization showed it responds to the heptapeptide core common to ACTH and α-, β-, and γ-MSH with increased intracellular cAMP; expression is in brain, placenta, and gut but not melanoma cells or adrenal gland. PCR-based cloning, pharmacological characterization (receptor binding and cAMP assay), Northern blot and PCR expression analysis The Journal of biological chemistry High 8463333
1993 A novel human melanocortin receptor (MC2, later also designated MC-2) was cloned; when expressed in COS-7 cells it bound [125I]-NDP-MSH and was displaced by α-, β-, γ-MSH and ACTH but not β-endorphin, with highest affinity for NDP-MSH (Ki ~5 nM); receptor is expressed in brain. Genomic cloning, COS-7 cell expression, radioligand binding displacement assay Biochemical and biophysical research communications High 8396929
1994 The mouse MC5 receptor (mMC5R) was cloned and shown to couple to adenylyl cyclase (cAMP increase) upon melanocortin stimulation; potency hierarchy was α-MSH > β-MSH > ACTH > γ-MSH; N- and C-terminal portions of α-MSH, but not the core heptapeptide alone, are key for MC5R activation. PCR-based cloning, cAMP assay in transfected cells, structure-activity analysis, Northern blot Biochemical and biophysical research communications High 8185570
1994 Structural modifications at Trp9 of ACTH (substitution with Phe or N-α-methyltryptophan) produce antagonists that bind the ACTH receptor with high affinity but fail to activate the adrenal cortical adenylate cyclase system, demonstrating that Trp9 is essential for receptor activation but not binding, and that receptor occupancy alone is insufficient for hormonal activity. In vitro adenylate cyclase assay with bovine adrenal cortical plasma membranes; structure-activity analysis with ACTH analogs Proceedings of the National Academy of Sciences of the United States of America High 4359333
1996 UVB radiation stimulates increased POMC gene expression accompanied by production and release of α-MSH and ACTH by normal and malignant human melanocytes and keratinocytes; this response is also stimulated by dbcAMP and IL-1α, and can be abolished by the free radical scavenger NAC, implicating a cyclic AMP-dependent pathway and oxidative stress in UVB-induced POMC peptide production. Cell culture of human melanocytes and keratinocytes; UVB irradiation; RIA for α-MSH and ACTH; pharmacological manipulation (dbcAMP, IL-1α, NAC) Biochimica et biophysica acta High 8781560
1997 None of the melanocortin receptors MC1, MC3, MC4, or MC5 possess binding epitopes for ACTH beyond the α-MSH sequence; MC3R shows >10-fold higher affinity for ACTH peptides than MC4R and favors the desacetylated N-terminus, suggesting MC3R as the likely mediator of short-loop negative feedback by ACTH/MSH peptides on CRF release. Competitive radioligand binding assay on transiently transfected eukaryotic cells expressing individual MCRs, using 125I-[Nle4,D-Phe7]α-MSH The Journal of endocrinology High 9390008
1998 Two human patients with compound heterozygous or homozygous mutations in POMC exons develop early-onset obesity, adrenal insufficiency, and red hair pigmentation, establishing POMC as a monogenic determinant of energy homeostasis, adrenal function, and skin/hair pigmentation in humans. POMC gene sequencing in patients; identification of mutations (G7013T, C7133Δ in exon 3; C3804A in exon 2) that impair ACTH and α-MSH synthesis or abolish POMC translation Nature genetics High 9620771
1998 The Arg151Cys variant of human MC1R binds α-MSH with normal affinity but cannot be stimulated to produce cAMP, rendering MC1R completely nonfunctional and explaining red hair, light skin, and poor tanning ability in affected individuals. Receptor binding with 131I-α-MSH; cAMP functional assay in transfected cells expressing Arg151Cys MC1R vs. wild-type Biochemical and biophysical research communications High 9571181
1999 Desacetyl-α-MSH activates MC1, MC3, MC4, and MC5 receptors (EC50 0.13–0.84 nM) with comparable or greater potency to α-MSH; mouse agouti protein antagonizes desacetyl-α-MSH coupling to MC4R much more effectively than α-MSH coupling (with reduced Bmax and increased EC50), revealing differential antagonism depending on the N-terminal acetylation state of the ligand. Stable expression of individual MCRs in HEK293 cells; PKA signaling pathway assay; competitive antagonism with agouti protein Endocrinology High 10218968
1999 Several common MC1R point mutations (Val60Leu, Arg142His, Arg151Cys, Arg160Trp, Asp294His) found in red-haired individuals lose the ability to stimulate cAMP in response to α-MSH without complete loss of ligand binding (Arg142His and Asp294His show slight reduction in binding affinity), demonstrating loss-of-function at the signaling level. Transfection of mutant MC1R constructs in COS-1 cells; radioligand binding; cAMP production assay Biochemical and biophysical research communications High 10403794
1999 Chicken POMC gene was isolated as a single-copy gene with the same structural organization as mammalian POMC; the predicted 251 aa POMC contains nine proteolytic cleavage sites and can give rise to all melanocortin family members (ACTH, α-, β-, γ-MSH) and β-endorphin; POMC mRNA is expressed in brain, adrenal gland, gonads, kidney, uropygial gland, and adipose tissue. Genomic library screening, molecular cloning, sequence analysis, RT-PCR expression profiling Biochimica et biophysica acta Medium 10395956
2002 A missense mutation R236G in POMC disrupts the dibasic cleavage site between β-MSH and β-endorphin; cells transfected with mutant POMC produce a β-MSH/β-endorphin fusion protein that binds hMC4R with normal affinity but has markedly reduced ability to activate it, establishing a novel mechanism of obesity susceptibility through production of an aberrant POMC product that interferes with melanocortin signaling. POMC gene sequencing in 262 obese subjects; transfection of mutant POMC cDNA in β-TC3 cells; metabolic labeling; receptor binding and cAMP assay with hMC4R Human molecular genetics High 12165561
2003 Leptin stimulates POMC gene transcription via activation of STAT3; leptin-induced POMC promoter activity requires the STAT3-binding site (Tyr1138) of the leptin receptor ObRb and a defined 30-bp promoter element; approximately 37% of hypothalamic POMC neurons (concentrated in the rostral region) show leptin-induced STAT3 phosphorylation. POMC promoter reporter assays in transfected cells; dominant-negative STAT3 expression; ObRb Tyr1138 mutant; double immunohistochemistry for phospho-STAT3 and POMC in rat hypothalamus Endocrinology High 12697721
2003 α-MSH and desacetyl-α-MSH similarly couple overexpressed MC1, MC3, MC4, and MC5 receptors to both adenylyl cyclase and calcium signaling pathways in HEK293 cells; however, α-MSH (but not desacetyl-α-MSH) significantly increases primary rat osteoblast proliferation, revealing a functional divergence at endogenous (low) receptor expression levels. Stably expressed MCRs in HEK293 cells; adenylyl cyclase assay; calcium signaling assay; primary osteoblast proliferation assay Annals of the New York Academy of Sciences Medium 12851298
2005 NPY inhibits posttranslational processing of POMC to active α-MSH by reducing prohormone convertase-2 (PC2) levels in ARC neurons; this is mediated through NPY-Y1 receptors and the transcription factor Egr-1. NPY also decreases α-MSH-induced CREB phosphorylation in the PVN, reducing TRH production, and decreases the amount of α-MSH delivered to PVN neurons. In vivo NPY injection; PC2 mRNA and protein measurements; Egr-1 knockdown; CREB phosphorylation assay; α-MSH and TRH measurements in hypothalamic nuclei American journal of physiology. Endocrinology and metabolism High 23321476
2005 CRH stimulates cAMP, POMC gene expression, ACTH production and release, and corticosterone production in human dermal fibroblasts (but not keratinocytes), demonstrating a functional cutaneous CRH-POMC-corticosteroid axis equivalent to the HPA axis. Primary human fibroblast and keratinocyte cultures; cAMP assay; POMC mRNA and protein measurement; ELISA for corticosterone Journal of neuroimmunology High 15833364
2005 LXRα positively regulates the POMC gene promoter at the transcriptional level; the RXRα/LXRα heterodimer binds the region between -73 and -52 bp of the rat POMC promoter; LXR agonist TO901317 increased POMC mRNA, ACTH immunoreactivity in pituitary, and plasma ACTH/corticosterone in vivo. Luciferase reporter assay; siRNA knockdown of LXRα; EMSA (electrophoretic mobility shift assay); chromatin immunoprecipitation (ChIP); in vivo mouse experiments Molecular endocrinology (Baltimore, Md.) High 19036902
2008 Two novel heterozygous missense mutations in the POMC N-terminus (C28F and L37F) impair sorting of POMC to the regulated secretory pathway, redirecting mutant POMC to the constitutive secretory pathway, thereby preventing normal propeptide processing to bioactive melanocortin products and causing early-onset obesity. Metabolic labeling, Western blotting, immunoassay of lysates and conditioned media of transiently transfected β-TC3 cells; comparison of wild-type vs. mutant POMC processing and secretion The Journal of clinical endocrinology and metabolism High 18697863
2010 POMC neuron-specific deletion of PTP1B reduces adiposity, improves leptin sensitivity, and increases energy expenditure on high-fat diet; POMC neuron-specific deletion of SHP2 produces opposite effects (increased adiposity, decreased leptin sensitivity, reduced energy expenditure) and markedly reduces hypothalamic POMC mRNA and α-MSH peptide levels, demonstrating that PTP1B and SHP2 reciprocally regulate energy balance via POMC neurons. Conditional (Cre-lox) POMC neuron-specific knockout mice for Ptp1b and Shp2; body composition measurement; hyperinsulinemic-euglycemic clamp; hypothalamic POMC mRNA and α-MSH peptide quantification The Journal of clinical investigation High 20160350
2013 Pharmacogenetic (DREADD) activation of NTS POMC neurons acutely inhibits feeding within minutes, while ARC POMC neurons require chronic stimulation to suppress food intake; ablation of ARC but not NTS POMC neurons with diphtheria toxin increases food intake, reduces energy expenditure, and causes obesity and endocrine disorders, demonstrating distinct temporal and functional roles for POMC neurons in the two brain regions. Cre-dependent AAV delivery of hM3Dq DREADD or diphtheria toxin receptor to ARC vs. NTS POMC neurons in POMC-Cre mice; clozapine-N-oxide administration; diphtheria toxin ablation; food intake and energy expenditure measurement The Journal of neuroscience : the official journal of the Society for Neuroscience High 23426689
2014 MeCP2 positively regulates hypothalamic Pomc expression by preventing promoter DNA hypermethylation; deletion of MeCP2 in POMC neurons increases DNA methylation of the Pomc promoter and reduces POMC expression, causing obesity and leptin resistance. In vitro, hypermethylation of the Pomc promoter reduces transcriptional activity, and MeCP2 acts synergistically with CREB1 to activate the Pomc promoter. POMC-neuron-specific MeCP2 knockout mice; bisulfite sequencing of Pomc promoter; luciferase reporter assay with methylated promoter; co-transfection with MeCP2 and CREB1; metabolic phenotyping Diabetologia High 24078059
2014 Early-life stress (maternal separation) reduces DNA methylation at a critical regulatory region (-417 to -260 bp) of the Pomc promoter in mouse pituitary, leading to increased Pomc mRNA that persists for up to 1 year. Methyl-CpG binding protein-2 (MeCP2) binds the distal Pomc promoter and acts with HDAC2 and DNMT1 to repress Pomc expression under basal conditions. Early-life stress model in mice; bisulfite sequencing; MeCP2 binding assay; AtT20 cell line with site-specific Pomc promoter methylation; co-immunoprecipitation of MeCP2 with HDAC2 and DNMT1 Endocrinology High 24506071
2015 FoxO1 inhibits STAT3-mediated leptin induction of POMC transcription through direct protein-protein interaction with STAT3; residues Gly140-Leu160 (specifically Gln145, Arg147, Lys148, Arg153, Arg154) of FoxO1 are critical for STAT3 binding; FoxO3 (but not FoxO4) similarly interacts with STAT3 and inhibits POMC promoter activity. Co-immunoprecipitation; FoxO1 deletion mutant analysis; POMC promoter luciferase assay; STAT3 binding mutants; computational docking simulation The Biochemical journal High 25510553
2015 GPR45 regulates POMC expression via the JAK/STAT signaling pathway in a cell-autonomous manner; disruption of Gpr45 in mice reduces POMC expression and energy expenditure; intraventricular melanotan-2 (α-MSH analog) rescues adult obesity in Gpr45 mutants, placing GPR45 upstream of POMC in the melanocortin energy-balance pathway. piggyBac insertional mutagenesis screen; conditional Gpr45 disruption; POMC expression measurement; JAK/STAT pathway analysis; intracerebroventricular drug administration; metabolic phenotyping The Journal of clinical investigation High 27500489
2015 Hypothalamic Kiss1 (kisspeptin) neurons, which regulate fertility and puberty onset, arise developmentally from POMC-expressing progenitors; using intersectional ribosome-tagging strategies in mice, Pomc-expressing precursors were shown to give rise to both energy-sensing POMC/AgRP neurons and reproductive Kiss1 neurons. Intersectional Cre-lox (embryonic and adult ribosome-tagging) transgenic mouse strategy; lineage tracing from Pomc-expressing progenitors; cell-type specific translational profiling The Journal of neuroscience : the official journal of the Society for Neuroscience High 25855171
2015 Metformin induces AMPK/LXRα phosphorylation followed by suppression of POMC expression in rat pituitary cells, leading to reduced ACTH and cortisol levels; this AMPK/LXRα/POMC pathway was confirmed in animal studies as a molecular mechanism underlying the antihyperglycemic effect of metformin. Urinary metabolomics in human subjects; in vitro rat pituitary cell treatment with metformin; AMPK and LXRα phosphorylation assays; POMC/ACTH measurement; in vivo rat experiments Scientific reports Medium 25634597
2016 E2F1 (phosphorylated at Ser-337) binds a cluster site in the proximal hPOMC promoter region (-42 to +68) and, together with its heterodimer partner DP1, drives ectopic hPOMC transcription in non-pituitary tumor cells independently of pituitary-specific Tpit/Pitx1 factors; inhibitors of E2F1 suppressed hPOMC expression and ACTH in vitro and in xenografted mice. POMC promoter reporter assays; E2F1/DP1 co-expression; ChIP for E2F1 binding; phosphorylation analysis (Ser-337); E2F1 inhibitors; xenograft mouse model; primary tumor cells Endocrine-related cancer High 27935805
2016 Glutamatergic ARC neurons expressing the oxytocin receptor rapidly cause satiety when optogenetically/chemogenetically activated; their projections converge with GABAergic AgRP projections on MC4R-expressing PVH neurons (PVHMC4R). Transmission across the ARCGlutamatergic→PVHMC4R synapse is potentiated by α-MSH (derived from ARCPOMC neurons) acting as an MC4R agonist, revealing post-synaptic modulation of a satiety circuit by POMC-derived α-MSH. Optogenetics and chemogenetics (DREADD); electrophysiology; circuit tracing; MC4R-Cre conditional mouse lines; synaptic physiology recording before and after α-MSH application Nature neuroscience High 27869800
2016 IRE1α in POMC neurons is required for thermogenesis and glycemia; POMC-specific Ire1α deficiency accelerates diet-induced obesity, impairs thermogenic responses and beiging of white adipose tissue, and causes whole-body glucose and insulin intolerance and hepatic insulin resistance; loss of Ire1α elevates ER stress and promotes leptin and insulin resistance in POMC neurons. Conditional Ire1α knockout in POMC neurons; metabolic phenotyping (energy expenditure, glucose/insulin tolerance tests, hepatic insulin sensitivity); hypothalamic ER stress markers Diabetes High 28028078
2017 TrpC5 channel subunits in POMC neurons mediate the acute anorexigenic effects of leptin and serotonin 2C receptor agonists; POMC-specific or neuronal TrpC5 deletion reduces energy expenditure, increases food intake, and blunts electrophysiological responses of arcuate POMC neurons to leptin and 5-HT2CR agonists, and blocks lorcaserin-induced glucose/insulin tolerance improvements. Conditional TrpC5 KO in POMC neurons; electrophysiology (patch-clamp) of arcuate POMC neurons; pharmacological challenge with leptin and 5-HT2CR agonist lorcaserin; metabolic phenotyping Cell reports High 28099839
2017 In diet-induced obese mice, persistently activated microglia hypersecrete TNFα which stimulates mitochondrial ATP production and fusion in POMC neuron neurites, increasing POMC neuronal firing rates and excitability; disruption of TNFα downstream signals TNFSF11A or NDUFAB1 in the mediobasal hypothalamus reverses mitochondrial elongation and reduces obesity. Diet-induced obesity mouse model; microglial activation characterization; TNFα measurement; mitochondrial morphology imaging in POMC neurons; electrophysiology; targeted gene disruption (TNFSF11A, NDUFAB1) Nature communications High 28489068
2017 DRP1-mediated mitochondrial fission in POMC neurons restrains leptin sensitivity and glucose sensing; inducible deletion of DRP1 in mature POMC neurons increases mitochondrial size, ROS production, and neuronal activation, improves leptin sensitivity and glucose responsiveness, and enhances glucoprivic counter-regulatory responses via PPAR-dependent upregulation of Kcnj11 (KATP channel subunit). Inducible conditional DRP1 KO in POMC neurons (Drp1fl/fl-POMC-cre:ERT2); mitochondrial morphology analysis; electrophysiology; leptin and glucose challenge assays; gene expression (Kcnj11, PPAR pathway) Cell metabolism High 28190775
2017 ATF4 in POMC neurons directly binds the ATG5 promoter and represses ATG5 transcription; loss of ATF4 in POMC neurons upregulates ATG5-dependent macroautophagy and increases α-MSH production in the hypothalamus, leading to a lean phenotype resistant to diet-induced obesity. Double KO of Atf4 and Atg5 in POMC neurons reverses the lean phenotype, placing ATG5/autophagy downstream of ATF4 as a mechanism regulating α-MSH production. POMC-neuron-specific Atf4 KO; double Atf4/Atg5 KO; ATF4 ChIP at ATG5 promoter; autophagy flux assays; α-MSH measurement; metabolic phenotyping Autophagy High 28350524
2018 A subpopulation of POMC neurons is activated by insulin via insulin receptor signaling, and represses hepatic glucose production (HGP); the proportion of POMC neurons activated by insulin is regulated by the phosphatase TCPTP, which is increased by fasting and degraded after feeding. Elevated TCPTP in obesity represses insulin-induced activation of POMC neurons and their ability to suppress HGP. POMC-neuron-specific TCPTP deletion in mice; electrophysiology of POMC neurons; hepatic glucose production measurement (hyperinsulinemic-euglycemic clamp); TCPTP protein level analysis in obesity and fasting/fed states eLife High 30230471
2021 POMCLepr+ and POMCGlp1r+ neuron subpopulations in the arcuate nucleus are largely nonoverlapping, exhibit distinct electrophysiological properties and anatomical distributions, differentially express receptors for energy-state hormones and neurotransmitters, and differ in their ability to suppress feeding, revealing a functional microarchitecture of POMC neurons. Intersectional Cre/Dre-dependent mouse models for labeling specific POMC subpopulations; translational profiling (RiboTag); electrophysiology; chemogenetic feeding assays Nature neuroscience High 34002087
2021 mTORC1 blockade in POMC neurons induces hyperphagia by mimicking a cellular negative energy state; this is associated with decreased α-MSH production, recruitment of POMC/GABAergic neurotransmission (restrained by cannabinoid type 1 receptor), and simultaneous activation of POMC/GABAergic neurons and inhibition of POMC/glutamatergic neurons, revealing mTORC1 as an orchestrator of functionally distinct POMC neuron subpopulations. Conditional mTORC1 (Raptor) KO in POMC neurons; chemogenetics; electrophysiology; optogenetics; α-MSH measurement; translational profiling and single-cell analysis Cell reports High 34644574
2021 In diabetic mice, NF-κB p50 subunit binding to the Pomc promoter represses POMC expression in sensory neurons; decreased POMC leads to lysosomal degradation of μ-opioid receptor (MOR), impairing antinociception; viral overexpression of POMC and MOR in sensory ganglia rescues the neuropathic pain phenotype. Streptozotocin diabetic mouse model; ChIP for NF-κB p50 at Pomc promoter; peripheral nerve POMC level measurement; MOR degradation analysis; AAV-mediated overexpression of POMC and MOR in sensory ganglia; behavioral pain assays; validation in human diabetic peripheral nervous system tissue Nature communications High 33462216
2021 L-Lactate activates hypothalamic POMC neurons via two mechanisms: (1) through HCAR1 (hydroxycarboxylic acid receptor 1) on astrocytes coupled to Gαi/o-protein, mediating intercellular signaling to POMC neurons; and (2) via intracellular action blocked by the lactate transporter inhibitor 4-CIN in a subset of POMC neurons; depolarization in both cases is pertussis toxin-sensitive. Patch-clamp electrophysiology of labeled POMC neurons; pharmacological dissection with PTX, 4-CIN, APJ receptor antagonist, HCAR1 agonist 3Cl-HBA; immunohistochemical localization of HCAR1 to astrocytes not POMC neurons Scientific reports Medium 34737351
2020 Optogenetic activation of the ARCPOMC→MeA (medial amygdala) neural projection reduces short-term food intake; anterograde tracing shows ARC POMC neurons project to ER-α- and MC4R-expressing neurons in the MeA; the anorectic effect of ARCPOMC→MeA stimulation is blocked by the MC4R antagonist SHU9119, establishing a functional extrahypothalamic melanocortinergic satiety circuit. Optogenetics (ChR2); monosynaptic anterograde and retrograde viral tracing; double immunohistochemistry for MC4R and ER-α; MC4R antagonist pharmacology; food intake measurement Frontiers in neural circuits High 33250721
2015 Apelin-13 depolarizes approximately half of arcuate POMC neurons in a dose-dependent manner via the APJ receptor; this effect is mediated by Gβγ-dependent activation of PLC-β signaling (not Gαi/o) that inhibits M-type current (KCNQ channels 2, 3, 5); pertussis toxin does not block the response, but the Gβγ inhibitor gallein and PLC/PKC inhibitors do. Electrophysiology (patch-clamp); single-cell qPCR for APJ receptor and KCNQ subunits; pharmacological dissection with APJ antagonist, pertussis toxin, gallein, PLC/PKC inhibitors; M-current measurement PloS one High 25782002

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
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2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2020 A reference map of the human binary protein interactome. Nature 849 32296183
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2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
1995 Initial assessment of human gene diversity and expression patterns based upon 83 million nucleotides of cDNA sequence. Nature 660 7566098
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
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2008 Many sequence variants affecting diversity of adult human height. Nature genetics 520 18391951
1994 Structural determinants for activation of the alpha-subunit of a heterotrimeric G protein. Nature 517 8208289
1995 The structure of an intermediate in class II MHC maturation: CLIP bound to HLA-DR3. Nature 505 7477400
2013 Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture. Nature genetics 496 23563607
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2017 Synergistic drug combinations for cancer identified in a CRISPR screen for pairwise genetic interactions. Nature biotechnology 378 28319085
2013 Acute and long-term suppression of feeding behavior by POMC neurons in the brainstem and hypothalamus, respectively. The Journal of neuroscience : the official journal of the Society for Neuroscience 366 23426689
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2006 Corticotropin-releasing factor within the central nucleus of the amygdala mediates enhanced ethanol self-administration in withdrawn, ethanol-dependent rats. The Journal of neuroscience : the official journal of the Society for Neuroscience 328 17079660
1993 Molecular cloning of a novel human melanocortin receptor. Biochemical and biophysical research communications 299 8396929
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1994 Molecular cloning, expression, and characterization of a fifth melanocortin receptor. Biochemical and biophysical research communications 277 8185570
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2006 Corticotropin-releasing factor 1 antagonists selectively reduce ethanol self-administration in ethanol-dependent rats. Biological psychiatry 243 16876134
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2016 A rapidly acting glutamatergic ARC→PVH satiety circuit postsynaptically regulated by α-MSH. Nature neuroscience 213 27869800
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1999 Loss of function mutations of the human melanocortin 1 receptor are common and are associated with red hair. Biochemical and biophysical research communications 198 10403794
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2002 A missense mutation disrupting a dibasic prohormone processing site in pro-opiomelanocortin (POMC) increases susceptibility to early-onset obesity through a novel molecular mechanism. Human molecular genetics 193 12165561
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2010 PTP1B and SHP2 in POMC neurons reciprocally regulate energy balance in mice. The Journal of clinical investigation 169 20160350
2006 Heterozygosity for a POMC-null mutation and increased obesity risk in humans. Diabetes 157 16936203
2002 Expression of autotaxin (NPP-2) is closely linked to invasiveness of breast cancer cells. Clinical & experimental metastasis 149 12498389
2017 CLIP Tool Kit (CTK): a flexible and robust pipeline to analyze CLIP sequencing data. Bioinformatics (Oxford, England) 142 27797762
2021 Functionally distinct POMC-expressing neuron subpopulations in hypothalamus revealed by intersectional targeting. Nature neuroscience 130 34002087
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2005 CRH stimulates POMC activity and corticosterone production in dermal fibroblasts. Journal of neuroimmunology 116 15833364
2000 Implications of proopiomelanocortin (POMC) mutations in humans: the POMC deficiency syndrome. Trends in endocrinology and metabolism: TEM 110 10652501
2011 Defining POMC neurons using transgenic reagents: impact of transient Pomc expression in diverse immature neuronal populations. Endocrinology 107 22166984
2008 Effects of non-human species irradiation after the Chernobyl NPP accident. Environment international 101 18234336
2018 Insulin regulates POMC neuronal plasticity to control glucose metabolism. eLife 99 30230471
2017 TNFα drives mitochondrial stress in POMC neurons in obesity. Nature communications 99 28489068
2006 Proopiomelanocortin (POMC): the cutaneous roles of its melanocortin products and receptors. Clinical and experimental dermatology 98 16681590
1998 Human pigmentation phenotype: a point mutation generates nonfunctional MSH receptor. Biochemical and biophysical research communications 98 9571181
2014 Early-life stress reduces DNA methylation of the Pomc gene in male mice. Endocrinology 97 24506071
2011 Evolution of POMC: origin, phylogeny, posttranslational processing, and the melanocortins. Annals of the New York Academy of Sciences 96 21388402
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2001 In situ expression of corticotropin-releasing hormone (CRH) and proopiomelanocortin (POMC) genes in human skin. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 91 11511529
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2017 TrpC5 Mediates Acute Leptin and Serotonin Effects via Pomc Neurons. Cell reports 82 28099839
2013 SNAP-, CLIP- and Halo-tag labelling of budding yeast cells. PloS one 82 24205303
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2012 AgRP and POMC neurons are hypophysiotropic and coordinately regulate multiple endocrine axes in a larval teleost. Cell metabolism 80 22245570
2017 DRP1 Suppresses Leptin and Glucose Sensing of POMC Neurons. Cell metabolism 77 28190775
2000 The role of alpha-MSH as a modulator of cutaneous inflammation. Annals of the New York Academy of Sciences 76 11268349
2014 PIPE-CLIP: a comprehensive online tool for CLIP-seq data analysis. Genome biology 75 24451213
2019 Chronic Low-grade Inflammatory Phenotype (CLIP) and Senescent Immune Dysregulation. Clinical therapeutics 74 30833113
2015 Fertility-regulating Kiss1 neurons arise from hypothalamic POMC-expressing progenitors. The Journal of neuroscience : the official journal of the Society for Neuroscience 74 25855171
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2016 60 YEARS OF POMC: Adrenal and extra-adrenal functions of ACTH. Journal of molecular endocrinology 72 26793988
2015 Antihyperglycemic mechanism of metformin occurs via the AMPK/LXRα/POMC pathway. Scientific reports 72 25634597
1999 alpha-MSH and the regulation of melanocyte function. Annals of the New York Academy of Sciences 70 10816655
2010 DNA methylation of the POMC gene promoter is associated with craving in alcohol dependence. Journal of neural transmission (Vienna, Austria : 1996) 68 20191296
2000 ARC POMC mRNA and PVN alpha-MSH are lower in obese relative to lean zucker rats. Brain research 67 10799663
2005 Effects of fasting, leptin, and insulin on AGRP and POMC peptide release in the hypothalamus. Brain research 66 15680952
2003 Adrenocortical zonation and ACTH. Microscopy research and technique 66 12768537
1999 UV light and MSH receptors. Annals of the New York Academy of Sciences 66 10816644
2011 Integrated systems for rapid point of care (PoC) blood cell analysis. Lab on a chip 64 21331413
2006 Hypothalamic proopiomelanocortin (POMC) neurons have a cholinergic phenotype. The European journal of neuroscience 63 17156199
1999 Molecular cloning and characterization of the chicken pro-opiomelanocortin (POMC) gene. Biochimica et biophysica acta 62 10395956
2008 Dietary resistant starch increases hypothalamic POMC expression in rats. Obesity (Silver Spring, Md.) 60 18948970
2015 Pro-Opiomelanocortin (POMC) Neurones, POMC-Derived Peptides, Melanocortin Receptors and Obesity: How Understanding of this System has Changed Over the Last Decade. Journal of neuroendocrinology 59 25872650
1999 ACTH resistance syndromes. Journal of pediatric endocrinology & metabolism : JPEM 56 10698592
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2005 Inherited ACTH insensitivity illuminates the mechanisms of ACTH action. Trends in endocrinology and metabolism: TEM 54 16271481
2012 The neuroendocrine circuitry controlled by POMC, MSH, and AGRP. Handbook of experimental pharmacology 52 22249810
2014 Leptin resistance and obesity in mice with deletion of methyl-CpG-binding protein 2 (MeCP2) in hypothalamic pro-opiomelanocortin (POMC) neurons. Diabetologia 51 24078059
2018 The Future of Cross-Linking and Immunoprecipitation (CLIP). Cold Spring Harbor perspectives in biology 48 30068528
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2004 Characterization of an adrenocorticotropin (ACTH) receptor promoter polymorphism leading to decreased adrenal responsiveness to ACTH. The Journal of clinical endocrinology and metabolism 44 15240582
2008 Mutations in the amino-terminal region of proopiomelanocortin (POMC) in patients with early-onset obesity impair POMC sorting to the regulated secretory pathway. The Journal of clinical endocrinology and metabolism 43 18697863
2013 A computational approach for identifying microRNA-target interactions using high-throughput CLIP and PAR-CLIP sequencing. BMC genomics 42 23368412
2016 Ire1α in Pomc Neurons Is Required for Thermogenesis and Glycemia. Diabetes 41 28028078
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2008 Early embryonic requirement for nucleoporin Nup35/NPP-19 in nuclear assembly. Developmental biology 40 19146848
2005 Hypomethylation in the promoter region of POMC gene correlates with ectopic overexpression in thymic carcinoids. The Journal of endocrinology 39 15845926
2021 Functional heterogeneity of POMC neurons relies on mTORC1 signaling. Cell reports 38 34644574
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2005 Novel 3D pharmacophore of alpha-MSH/gamma-MSH hybrids leads to selective human MC1R and MC3R analogues. Journal of medicinal chemistry 36 15771429
2021 Lactate activates hypothalamic POMC neurons by intercellular signaling. Scientific reports 35 34737351
2016 Disruption of Gpr45 causes reduced hypothalamic POMC expression and obesity. The Journal of clinical investigation 34 27500489
2013 Mechanisms by which the orexigen NPY regulates anorexigenic α-MSH and TRH. American journal of physiology. Endocrinology and metabolism 34 23321476
1974 ACTH antagonists. Proceedings of the National Academy of Sciences of the United States of America 34 4359333
2014 Clinical utility of plasma POMC and AgRP measurements in the differential diagnosis of ACTH-dependent Cushing's syndrome. The Journal of clinical endocrinology and metabolism 33 25013995
2000 The neuropeptide alpha-MSH in host defense. Annals of the New York Academy of Sciences 33 11268348
2005 Circumventing central leptin resistance: lessons from central leptin and POMC gene delivery. Peptides 32 16274846
2018 POMC Neurons: Feeding, Energy Metabolism, and Beyond. Advances in experimental medicine and biology 30 30390283
2016 ACTH Antagonists. Frontiers in endocrinology 29 27547198
2016 E2F1-mediated human POMC expression in ectopic Cushing's syndrome. Endocrine-related cancer 29 27935805
2014 CLIP-170 recruits PLK1 to kinetochores during early mitosis for chromosome alignment. Journal of cell science 29 24777477
2018 GoldCLIP: Gel-omitted Ligation-dependent CLIP. Genomics, proteomics & bioinformatics 28 29709556
2015 FoxO1 negatively regulates leptin-induced POMC transcription through its direct interaction with STAT3. The Biochemical journal 27 25510553
2000 Pro-opiomelanocortin (POMC) deficiency and peripheral melanocortins in obesity. Nutrition reviews 27 10885325
2021 COVID-19 Biomarkers and Advanced Sensing Technologies for Point-of-Care (POC) Diagnosis. Bioengineering (Basel, Switzerland) 26 34356205
2020 Detection and Quantification of HspX Antigen in Sputum Samples Using Plasmonic Biosensing: Toward a Real Point-of-Care (POC) for Tuberculosis Diagnosis. ACS infectious diseases 25 32233503
2015 60 YEARS OF POMC: POMC: an evolutionary perspective. Journal of molecular endocrinology 25 26671895
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1983 Multiple factors involved in the control of ACTH and alpha-MSH secretion. Journal of steroid biochemistry 25 6310240
2015 Apelin-13 enhances arcuate POMC neuron activity via inhibiting M-current. PloS one 24 25782002
1999 Agouti antagonism of melanocortin-4 receptor: greater effect with desacetyl-alpha-melanocyte-stimulating hormone (MSH) than with alpha-MSH. Endocrinology 24 10218968
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2021 Loss of POMC-mediated antinociception contributes to painful diabetic neuropathy. Nature communications 23 33462216
2020 Activation of the ARCPOMC→MeA Projection Reduces Food Intake. Frontiers in neural circuits 23 33250721
2017 An ATF4-ATG5 signaling in hypothalamic POMC neurons regulates obesity. Autophagy 23 28350524
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2021 The Impact of Recent Developments in Electrochemical POC Sensor for Blood Sugar Care. Frontiers in chemistry 22 34395386
2015 60 YEARS OF POMC: The proopiomelanocortin gene: discovery, deletion and disease. Journal of molecular endocrinology 22 26643913
2014 HITS-CLIP (CLIP-Seq) for mouse Piwi proteins. Methods in molecular biology (Clifton, N.J.) 22 24178558
2008 Liver X receptor-alpha regulates proopiomelanocortin (POMC) gene transcription in the pituitary. Molecular endocrinology (Baltimore, Md.) 22 19036902
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2003 alpha-MSH and desacetyl-alpha-MSH signaling through melanocortin receptors. Annals of the New York Academy of Sciences 22 12851298
2014 HITS-CLIP and PAR-CLIP advance viral miRNA targetome analysis. Critical reviews in eukaryotic gene expression 21 24940765