Affinage

POU1F1

Pituitary-specific positive transcription factor 1 · UniProt P28069

Length
291 aa
Mass
32.9 kDa
Annotated
2026-04-28
100 papers in source corpus 35 papers cited in narrative 34 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

POU1F1 (Pit-1/GHF-1) is a pituitary-specific POU-homeodomain transcription factor that serves as a master regulator of anterior pituitary cell-type specification and hormone gene expression, with an additional oncogenic role in breast cancer. Its homeodomain mediates sequence-specific DNA binding — stimulated but not directly contacted by the POU-specific domain — while a hydroxylated-residue-rich N-terminal domain drives transcriptional activation; phosphorylation at Thr220 by PKA/PKC differentially modulates DNA binding affinity in a promoter-context-dependent manner (enhancing TSHβ binding while reducing GH/PRL binding), and signal-dependent switching between N-CoR/SMRT/HDAC co-repressor and CBP/p300/pCAF co-activator complexes controls transcriptional output (PMID:2902927, PMID:2574416, PMID:1652153, PMID:1321428, PMID:9751061). POU1F1 determines pituitary cell fate through reciprocal interaction with GATA2, suppressing the gonadotrope program via DNA binding-independent inhibition of GATA2, while alternative splicing generates functionally distinct isoforms including a dominant-negative beta isoform and a thyrotrope-specific Pit-1T required for TSHβ activation (PMID:10367888, PMID:1569967, PMID:8407911). Loss-of-function mutations in POU1F1 — affecting DNA binding, dimerization, or CBP recruitment — cause combined pituitary hormone deficiency (CPHD), and variants favoring the repressive beta isoform act in a dominant-negative manner (PMID:16263824, PMID:15928241, PMID:34270938). In breast cancer, POU1F1 directly transactivates SNAI1, MMP-13, and LDHA to drive epithelial–mesenchymal transition, invasion, and metabolic reprogramming toward aerobic glycolysis, and recruits tumor-associated macrophages via CXCL12 (PMID:21060149, PMID:25527274, PMID:33714987, PMID:31292963).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1988 High

    The identity of the trans-acting factor controlling pituitary GH expression was unknown; cloning of GHF-1 established it as a homeodomain-containing, pituitary-specific transcription factor whose homeodomain mediates DNA binding, founding the POU family paradigm.

    Evidence cDNA cloning and DNase I footprinting with bacterially expressed protein

    PMID:2902927

    Open questions at the time
    • Full domain architecture and activation mechanism undefined
    • Relationship between POU-specific domain and homeodomain unclear
  2. 1989 High

    The functional architecture of Pit-1 was dissected: the homeodomain alone is sufficient for sequence-specific binding (with the POU-specific domain enhancing but not directly contacting DNA), while a separate hydroxylated-residue-rich N-terminal domain mediates transcriptional activation; purified Pit-1 shows promoter selectivity, binding GH but not PRL promoter sequences.

    Evidence Deletion mutagenesis with DNA binding and transcription assays; purified protein gel-shift and activation assays

    PMID:2563596 PMID:2574416

    Open questions at the time
    • How promoter selectivity is achieved at the structural level
    • Whether post-translational modifications tune binding specificity
  3. 1991 High

    Post-translational regulation of Pit-1 was revealed: phosphorylation at Thr220 in the POU homeodomain by PKA/PKC alters DNA-binding conformation in a flanking-sequence-dependent manner, providing a mechanism for signal-dependent differential gene regulation; simultaneously, Pit-1 binding sites were shown to mediate TRH responsiveness of the PRL promoter.

    Evidence Phosphorylation assays with site-directed mutagenesis of Thr220, DNase I footprinting; deletion mapping and mutagenesis of PRL promoter elements

    PMID:1652153 PMID:1922085

    Open questions at the time
    • Which kinase acts in vivo in each pituitary cell type
    • How phosphorylation is reversed
  4. 1992 High

    Phosphorylation was shown to have opposite effects on different target genes: PKA/PKC-mediated phosphorylation enhances Pit-1 binding to TSHβ elements 3–8-fold while reducing GH/PRL binding, explained by a single nucleotide difference in the core consensus; concurrently, alternative splicing was found to generate a beta isoform with a 26-amino-acid insert that abolishes PRL promoter transactivation, and activin was shown to repress GH by inhibiting Pit-1 DNA binding.

    Evidence In vitro kinase/gel-shift assays, reporter assays; cDNA cloning with DNA mobility shift and CAT assays; nuclear factor binding and transfection assays

    PMID:1321428 PMID:1454833 PMID:1561093 PMID:1569967

    Open questions at the time
    • Physiological balance between isoforms in individual cell types
    • Mechanism by which activin inhibits Pit-1 binding
  5. 1993 High

    Lineage determination and isoform specialization were established: GHF-1 regulatory sequences drive expression in somatotropic progenitors before GH or PRL onset, and a thyrotrope-specific Pit-1T isoform (14-aa insert) is required for TSHβ promoter activation, demonstrating isoform-specific cell-fate functions.

    Evidence Transgenic mouse models with lineage-targeted oncogenes; RT-PCR, Western blot, and reporter assays in thyrotrope cell lines

    PMID:8096199 PMID:8407911

    Open questions at the time
    • Upstream signals controlling isoform switching
    • Whether Pit-1T has targets beyond TSHβ
  6. 1995 High

    Multi-level regulation of Pit-1 was deepened: activin increases Pit-1 phosphorylation and accelerates protein degradation while only moderately reducing synthesis, and systematic mutagenesis identified critical POU-domain residues; the N-terminal transactivation domain was mapped as the specific target for dopaminergic inhibitory signaling.

    Evidence Pulse-chase and stability assays in somatotropes; random mutagenesis screen in yeast; chimeric LexA-Pit-1 constructs with G-alpha gain-of-function mutants

    PMID:7499395 PMID:7592721 PMID:7706253

    Open questions at the time
    • Proteasomal versus other degradation pathways not defined
    • Molecular identity of the inhibitory signal transducer
  7. 1998 High

    The coregulator switch model was established: Pit-1 activity is determined by a regulated balance between N-CoR/SMRT/HDAC co-repressor and CBP/pCAF co-activator complexes, with cAMP and growth-factor pathways requiring distinct CBP domains and HAT activities; live-cell FRET confirmed Pit-1 dimerization and interaction with c-Ets-1.

    Evidence Co-immunoprecipitation, HAT activity assays, dominant-negative mutants; FRET microscopy with GFP/BFP fusions in living cells

    PMID:9731708 PMID:9751061

    Open questions at the time
    • Chromatin remodeling dynamics at endogenous loci not resolved
    • Whether dimerization is required at all target promoters
  8. 1999 High

    Pit-1's role in cell-fate determination was mechanistically refined: it suppresses the GATA2-dependent gonadotrope program by DNA-binding-independent inhibition of GATA2 at gonadotrope-specific genes, establishing reciprocal Pit-1/GATA2 interactions as molecular memory of developmental signaling gradients; the POU-specific domain was also found to contain a nuclear matrix targeting signal whose dynamic partitioning is required for transactivation.

    Evidence Genetic epistasis in mouse pituitary, ChIP, DNA binding assays; biochemical fractionation and mutagenesis of nuclear matrix targeting

    PMID:10022514 PMID:10367888

    Open questions at the time
    • Structural basis of DNA-binding-independent GATA2 inhibition unknown
    • Functional significance of nuclear matrix association at endogenous loci
  9. 2005 High

    Structure–function links to disease were systematically defined: CPHD-causing mutations disrupt specific mechanisms — A158P/K216E impair CBP/p300 recruitment, R271W alters dimerization, and additional mutations differentially affect DNA binding versus transactivation; LHX4 was positioned upstream, directly binding the POU1F1 regulatory region.

    Evidence Gel-shift, CBP binding assays, cotransfection reporters for multiple patient mutations; recombinant LHX4 binding and transcription assays

    PMID:15928241 PMID:15998782 PMID:16263824

    Open questions at the time
    • No crystal structure of full-length POU1F1 with cofactors
    • Genotype–phenotype correlation for severity of CPHD incomplete
  10. 2015 High

    A transactivation-domain mutation (Pro76Leu) revealed post-transcriptional regulation: it selectively alters DNA binding at GH locus control region sites and enhances cofactor interactions (PITX1, LHX3a, ELK1), yet causes dramatically reduced protein levels in knock-in mice despite normal mRNA, pointing to protein stability as a key regulatory layer.

    Evidence Bandshift assays, co-immunoprecipitation, knock-in mouse model with protein/mRNA quantification

    PMID:26612202

    Open questions at the time
    • Degradation pathway responsible for reduced protein levels not identified
    • Whether cofactor interaction changes are cause or consequence of altered stability
  11. 2014 High

    POU1F1's oncogenic functions in breast cancer were mechanistically defined beyond pituitary biology: it directly occupies MMP-13 and SNAI1 promoters to drive invasion and EMT, and overexpression induces metastasis in xenografts that is completely blocked by MMP-13 knockdown.

    Evidence ChIP, luciferase reporter assays, siRNA knockdown, SCID mouse xenograft model

    PMID:21060149 PMID:25527274

    Open questions at the time
    • How POU1F1 is ectopically expressed in breast tissue is unclear
    • Whether POU1F1 cooperates with the same cofactors (CBP, N-CoR) in breast cancer as in pituitary
  12. 2021 High

    POU1F1's metabolic and splicing-based regulatory dimensions were uncovered: it directly transactivates LDHA to reprogram breast cancer metabolism toward aerobic glycolysis (with lactate promoting fibroblast activation), and systematic splicing assays revealed 96 splice-disruptive variants including synonymous ones that shift isoform balance toward the dominant-negative beta form, causing CPHD.

    Evidence ChIP on LDHA promoter, xenograft with FDG-PET imaging; high-throughput splicing reporter assay of 1,070 SNVs with minigene validation and patient co-segregation

    PMID:33714987 PMID:34270938

    Open questions at the time
    • Whether LDHA regulation occurs in pituitary or is breast cancer-specific
    • Functional consequences of many splice-disruptive variants beyond isoform ratio remain untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major unresolved questions include the structural basis of POU1F1's DNA-binding-independent inhibition of GATA2, the molecular mechanism linking POU1F1 to CXCL12 secretion in breast cancer, whether pituitary and breast cancer cofactor complexes overlap, and the in vivo determinants of POU1F1 protein stability.
  • No high-resolution structure of full-length POU1F1 in complex with cofactors or GATA2
  • Degradation pathway controlling POU1F1 protein turnover undefined
  • Mechanism of POU1F1 ectopic expression in breast cancer unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 8 GO:0003677 DNA binding 6
Localization
GO:0005634 nucleus 2 GO:0005654 nucleoplasm 1
Pathway
R-HSA-74160 Gene expression (Transcription) 8 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-1266738 Developmental Biology 2
Partners
CBPELK1ETS1GATA2LHX3NCOR1NCOR2PITX1

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1988 GHF-1 (POU1F1) is a homeobox-containing pituitary-specific transcription factor; the homeodomain region functions as its DNA binding domain, as demonstrated by DNase I footprinting with bacterially expressed fusion protein containing the GHF-1 homeodomain fragment. cDNA cloning, DNase I footprinting with bacterially expressed fusion protein Cell High 2902927
1989 The GHF-1 (POU1F1) homeodomain is sufficient for sequence-specific DNA binding, with activity stimulated by the POU-specific domain (which does not directly contact DNA), while transcriptional activation is mediated by a separate domain rich in hydroxylated amino acids. Deletion mutagenesis, in vitro DNA binding assays, transcription assays Nature High 2574416
1989 Purified GHF-1 (POU1F1) binds to and activates the GH promoter but does not recognize the prolactin promoter, demonstrating promoter selectivity; a distinct factor in pituitary extracts binds prolactin but not GH promoter sequences. Protein purification, gel mobility shift, transcription activation assays, antibody studies Science High 2563596
1991 Pit-1 (POU1F1) is phosphorylated at two distinct sites in pituitary cells in response to phorbol esters and cAMP; phosphorylation alters Pit-1 conformation on DNA, increasing binding at some response elements and decreasing it at others depending on flanking DNA sequences. Thr220 in the POU homeodomain is the key residue conferring these responses. Phosphorylation assays, DNase I footprinting, site-directed mutagenesis (Thr220) Science High 1652153
1992 Phosphorylation of Pit-1 by protein kinase A or C enhances its binding to TSHβ gene elements 3- to 8-fold, whereas phosphorylation generally reduces binding to prolactin and GH gene elements, due to a single nucleotide difference in the core binding consensus between TSHβ elements and PRL/GH elements. In vitro phosphorylation, gel mobility shift assays, transfection reporter assays Proceedings of the National Academy of Sciences of the United States of America High 1321428
1992 An alternatively spliced Pit-1 isoform (Pit-1 beta/Pit-1a) containing a 26 amino acid insert in the transactivation domain binds Pit-1 sites with markedly different DNA-protein complex mobility and is unable to transactivate the prolactin promoter (transactivation ratio <0.05 vs wild-type), demonstrating that the insert abrogates both DNA binding mode and transactivation. cDNA cloning, Southern blot, DNA mobility shift assays, stable transfection CAT reporter assays Nucleic acids research / Molecular endocrinology High 1561093 1569967
1991 Thyrotropin-releasing hormone (TRH) action on the prolactin promoter is mediated by Pit-1 binding to specific response elements (sites 1P and 3P); mutations abolishing Pit-1 binding to these sites eliminate the TRH response. Deletion mapping, oligonucleotide transfer assays, site-directed mutagenesis, transient transfection Molecular endocrinology High 1922085
1992 Activin A inhibits binding of Pit-1 to the GH promoter in somatotropic cells, mediating activin-induced repression of GH biosynthesis at the level of tissue-specific transcription factor binding. Nuclear factor binding assays, transfection of GH promoter-CAT fusion genes, deletion mapping Proceedings of the National Academy of Sciences of the United States of America High 1454833
1993 A thyrotrope-specific alternatively spliced variant of Pit-1 (Pit-1T), with a 14-amino acid insert in the transactivation domain, is required for TSHβ promoter stimulation; both Pit-1 and Pit-1T are required for TSHβ promoter activity in thyrotrope cells. RT-PCR, Western blot, transient transfection reporter assays in TtT-97 and alpha-TSH cell lines The Journal of biological chemistry High 8407911
1993 The GHF-1 (POU1F1) regulatory region is sufficient to drive somatotropic lineage-specific expression in transgenic mice; GHF-1 is expressed before GH or PRL in a somatotropic progenitor cell, and an enhancer driving GHF-1 transcription at this early stage is inactive in more differentiated cells. Transgenic mouse model (SV40 T-antigen targeting), immortalized cell lines, enhancer analysis Genes & development High 8096199
1993 Pit-1 activates pituitary renin gene expression by binding to a conserved sequence in the human renin 5'-flanking region; mutation of the Pit-1 binding site abolishes activation, and Pit-1 expression in HeLa cells activates the renin promoter in a site-dependent manner. Gel mobility shift, deletion and mutational analysis, Pit-1 expression vector cotransfection in HeLa cells The Journal of biological chemistry Medium 8420924
1994 Multiple Pit-1 binding sites throughout the proximal and distal regions of the rat PRL gene facilitate estrogen responsiveness; the most critical site is adjacent to the estrogen receptor-binding site in the distal enhancer; physical interaction between estrogen receptor and Pit-1 is largely DNA-dependent, as demonstrated by GST pulldown. Site-directed mutagenesis of Pit-1 binding sites, transient transfection, GST pulldown protein interaction assay Molecular endocrinology Medium 7708061
1995 In vivo mutagenesis screen in Saccharomyces cerevisiae identified point mutations in both the POU-specific and POU homeodomain of Pit-1 that alter DNA binding function; key residues include those in the hydrophobic core and those making direct DNA contacts. Random in vitro mutagenesis, functional screening in S. cerevisiae The Journal of biological chemistry High 7592721
1995 The N-terminal transactivation domain of Pit-1 (residues 8–80) is sufficient to mediate dopaminergic inhibition of prolactin gene transcription in endocrine cell types, acting as a specific target for inhibitory G protein signals via a cell-type-specific mechanism. Chimeric LexA-Pit-1 constructs, transient transfection in pituitary GH4 and islet RIN cells, G-alpha gain-of-function mutants The Journal of biological chemistry Medium 7706253
1995 Pit-1 exhibits a bimodal distance requirement for activation and synergism: transcription activity is highly sensitive to spacing between the Pit-1 binding site and the TATA box, with an optimum at −36 that rapidly declines but recovers at −56 in the prolactin promoter. Spacing mutation templates in an in vitro transcription system, transient transfection in GH3 cells The Journal of biological chemistry Medium 7876215
1995 Activin increases Pit-1 phosphorylation rapidly (temporally correlated with decreased GH DNA binding) and markedly decreases Pit-1 protein stability (degradation rate increased after >4 h), while only moderately reducing Pit-1 synthesis, demonstrating multilevel regulation of Pit-1 by activin. Pulse-chase phosphorylation assays, stability/synthesis assays, DNA binding assays in MtTW15 somatotrope cells The Journal of biological chemistry High 7499395
1996 Pit-1 regulates TRβ2 isoform promoter activity in pituitary thyrotropes and somatotropes through binding to multiple cis-acting elements; site-directed mutagenesis that abolishes Pit-1 binding reduces TRβ2 promoter activity, and Pit-1 expression reconstitutes activity in cells lacking it. DNase I footprinting, deletion analysis, site-directed mutagenesis, Pit-1 cotransfection reconstitution in alpha-TSH cells The Journal of biological chemistry High 8798664
1998 Pit-1 activity is determined by a regulated balance between a co-repressor complex (N-CoR/SMRT, mSin3A/B, histone deacetylases) and a co-activator complex (CBP and p/CAF); cAMP-stimulated Pit-1 activation requires the amino-terminal domain of CBP and p/CAF histone acetyltransferase activity, while growth factor-stimulated activation requires distinct carboxy-terminal domains of CBP and CAF histone acetyltransferase activity. Co-immunoprecipitation, domain mapping, HAT activity assays, dominant-negative mutants, reporter assays Nature High 9751061
1998 Pit-1 forms dimers when interacting with specific DNA elements; FRET microscopy in living cells demonstrates physical interaction between Pit-1 molecules and between Pit-1 and c-Ets-1, but no FRET signal was detected between Pit-1 and estrogen receptor. FRET microscopy with GFP/BFP fusion proteins in living HeLa cells, functional assays of fusion proteins Molecular endocrinology High 9731708
1999 Pit-1 mediates determination of pituitary cell types through both DNA binding-dependent functions and a DNA binding-independent function: Pit-1 suppresses the GATA2-dependent gonadotrope program by inhibiting GATA2 binding to gonadotrope-specific (but not thyrotrope-specific) genes without itself binding DNA at those sites; reciprocal interactions between Pit-1 and GATA2 serve as molecular memory of transient signaling gradients. Genetic epistasis in mouse pituitary development, chromatin immunoprecipitation, DNA binding assays, dominant-negative and loss-of-function experiments Cell High 10367888
1999 The POU-specific domain of Pit-1 contains a necessary and sufficient nuclear matrix targeting signal; inactive point mutants are completely matrix-bound regardless of DNA binding ability, suggesting that dynamic partitioning of Pit-1 between detergent-soluble and nuclear matrix-bound fractions is required for normal transactivator function. Biochemical fractionation (detergent extraction), in situ assays, deletion mutant and point mutant analysis, chimeric fusions Journal of cellular biochemistry Medium 10022514
2002 The W193R mutation in the POU-specific domain of POU1F1 causes a 500-fold reduction in DNA binding and transactivation; a 1-bp deletion (747delA) causes a frameshift producing a truncated protein lacking the DNA recognition helix of the POU homeodomain, resulting in loss of DNA binding. Functional characterization of patient mutations by gel shift/DNA binding assays and transcriptional activation assays The Journal of clinical endocrinology and metabolism High 11297581
2002 GST interaction studies show that only the homeodomain of Pit-1 (not the POU-specific domain or hinge region) directly interacts with GATA-2; multiple Pit-1 domains and specific spacing between Pit-1 and GATA-2 binding sites on the TSHβ promoter are required for full transcriptional synergy, with the two factors forming a ternary complex on the promoter. GST pulldown interaction assays, Pit-1 deletion mutant cotransfection, EMSA ternary complex formation assays Molecular and cellular endocrinology High 12385825
2005 CBP/p300 recruitment and Pit-1 dimerization are both required for Pit-1 target gene activation; specific CPHD-causing mutations (A158P, K216E) impair CBP/p300 binding, while R271W alters dimerization (binding as monomer with high avidity), and K216E enhances dimer binding—these defects account for loss of transactivation. Gel-shift studies, CBP/p300 binding assays, cotransfection reporter assays with GH and prolactin reporters The Journal of clinical endocrinology and metabolism High 16263824
2005 LHX4 directly binds to and activates transcription from the POU1F1 upstream regulatory sequence; mutant LHX4 proteins from patients with GH deficiency fail to bind and activate the POU1F1 regulatory sequence, establishing an LHX4→POU1F1→GH transcriptional pathway. Recombinant protein-DNA binding assays, transcription activation assays in CHO cells, comparison of wild-type vs. patient-derived mutant LHX4 The Journal of clinical endocrinology and metabolism High 15998782
2005 POU1F1 mutations E230K, R172Q, and ins778A are associated with CPHD: E230K reduces transactivation but not DNA binding; R172Q reduces both DNA binding and transactivation; ins778A abolishes DNA binding and reduces transactivation. DNA-binding assays, transactivation reporter assays for each mutant POU1F1 The Journal of clinical endocrinology and metabolism High 15928241
2008 PIT1 in TSHβ promoter regulation acts by counteracting suppression by a SR-binding factor: PIT1 does not synergize with GATA2 by conventional co-activation but instead prevents the inhibition of GATA2 transactivation by a suppressor region (nt −82/−52) through competition with an SR-binding nuclear factor, as demonstrated by EMSA showing PIT1 blocks SR-binding protein interaction. Deletion/mutational analysis of TSHβ promoter, cotransfection in CV1 cells, EMSA with recombinant PIT1 and nuclear extracts Journal of molecular endocrinology Medium 19103719
2010 Pit-1 overexpression in human breast cancer cells induces tumor growth and metastasis in immunodeficient mice; some pro-tumorigenic effects are mediated by upregulation of Snai1, an inducer of epithelial-mesenchymal transition. Knockdown of Pit-1 reverses these phenotypes. Overexpression and knockdown in human breast cancer cell lines, xenograft mouse model, protein expression profiling The Journal of clinical investigation Medium 21060149
2015 The Pro76Leu mutation in the POU1F1 transactivation domain selectively alters DNA binding affinity to hGH-LCR and hGH1 promoter sites (but not PRL promoter sites), enhances interactions with cofactors PITX1, LHX3a, and ELK1 as shown by co-immunoprecipitation, and causes dramatically reduced protein levels in knock-in mice despite normal mRNA. Bandshift assays, co-immunoprecipitation, knock-in mouse model, protein expression analysis Human molecular genetics High 26612202
2014 Pit-1 directly transcriptionally regulates MMP-1 and MMP-13 in breast cancer cells, as shown by ChIP and luciferase reporter assays; knockdown of MMP-13 completely blocks lung metastasis in Pit-1-overexpressing breast cancer xenografts. ChIP assay, luciferase reporter assay, siRNA knockdown, SCID mouse tumor xenograft model Breast cancer research High 25527274
2019 POU1F1 in breast cancer cells mediates recruitment and polarization of macrophages into tumor-associated macrophages (TAMs) through the release of CXCL12; TAMs in turn promote tumor growth, angiogenesis, and metastasis to lung. In vitro paracrine assays, zebrafish and mouse in vivo models, CXCL12 knockdown, human breast cancer patient samples The Journal of pathology Medium 31292963
2021 POU1F1 transcriptionally regulates the LDHA gene in breast cancer cells, driving metabolic reprogramming toward aerobic glycolysis; lactate produced through POU1F1→LDHA promotes cancer cell proliferation, migration, invasion, and fibroblast activation into cancer-associated fibroblasts. LDHA knockdown in POU1F1-overexpressing cells decreases tumor volume in xenografts. Transcriptional reporter assays, ChIP, siRNA knockdown, xenograft mouse model with [18F]FDG PET imaging, primary human breast tumor cultures Oncogene High 33714987
2021 Heterozygous missense variants that shift POU1F1 splicing to favor the beta isoform (which acts as a transcriptional repressor) cause dominant-negative loss of function; high-throughput splicing reporter assay identified 96 splice-disruptive POU1F1 variants including 14 synonymous ones, defining the landscape of splicing-sensitive positions. High-throughput splicing reporter assay (1,070 SNVs tested), minigene assays, functional repressor assays, patient co-segregation analysis American journal of human genetics High 34270938
2016 Leptin signaling through its receptor in somatotropes controls POU1F1 protein levels and all POU1F1-dependent hormones (GH, PRL, TSH) in a sex-specific manner; female but not male Lepr-null somatotropes show reduced POU1F1 protein despite normal mRNA, implicating post-transcriptional regulation by leptin. Cre-LoxP conditional knockout, fluorescence-activated cell sorting of purified somatotropes, enzyme immunoassays, qPCR Endocrinology Medium 27571135

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1988 The pituitary-specific transcription factor GHF-1 is a homeobox-containing protein. Cell 691 2902927
2006 Role of the sodium-dependent phosphate cotransporter, Pit-1, in vascular smooth muscle cell calcification. Circulation research 359 16527991
1992 Cretinism with combined hormone deficiency caused by a mutation in the PIT1 gene. Nature genetics 273 1302000
1998 Signal-specific co-activator domain requirements for Pit-1 activation. Nature 240 9751061
1999 Reciprocal interactions of Pit1 and GATA2 mediate signaling gradient-induced determination of pituitary cell types. Cell 239 10367888
1989 Dissection of functional domains of the pituitary-specific transcription factor GHF-1. Nature 218 2574416
1991 Variable effects of phosphorylation of Pit-1 dictated by the DNA response elements. Science (New York, N.Y.) 192 1652153
2002 The Snell dwarf mutation Pit1(dw) can increase life span in mice. Mechanisms of ageing and development 165 11718806
1992 Mutations in the Pit-1 gene in children with combined pituitary hormone deficiency. Biochemical and biophysical research communications 140 1472057
2013 Spironolactone ameliorates PIT1-dependent vascular osteoinduction in klotho-hypomorphic mice. The Journal of clinical investigation 133 23298834
2006 Enhanced expression of the inorganic phosphate transporter Pit-1 is involved in BMP-2-induced matrix mineralization in osteoblast-like cells. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 126 16734382
1993 GHF-1-promoter-targeted immortalization of a somatotropic progenitor cell results in dwarfism in transgenic mice. Genes & development 121 8096199
2007 Osteoblast autonomous Pi regulation via Pit1 plays a role in bone mineralization. Molecular and cellular biology 105 17438129
1989 Purification of growth hormone-specific transcription factor GHF-1 containing homeobox. Science (New York, N.Y.) 105 2563596
2016 Silent subtype 3 pituitary adenomas are not always silent and represent poorly differentiated monomorphous plurihormonal Pit-1 lineage adenomas. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 102 26743473
2009 Identification of a novel function of PiT1 critical for cell proliferation and independent of its phosphate transport activity. The Journal of biological chemistry 98 19726692
2010 Phosphate and vascular calcification: Emerging role of the sodium-dependent phosphate co-transporter PiT-1. Thrombosis and haemostasis 94 20664908
1992 Hormonal regulation of the thyrotropin beta-subunit gene by phosphorylation of the pituitary-specific transcription factor Pit-1. Proceedings of the National Academy of Sciences of the United States of America 94 1321428
1992 Functional isoforms of Pit-1 generated by alternative messenger RNA splicing. Molecular endocrinology (Baltimore, Md.) 94 1569967
1998 Visualization of Pit-1 transcription factor interactions in the living cell nucleus by fluorescence resonance energy transfer microscopy. Molecular endocrinology (Baltimore, Md.) 91 9731708
1998 Molecular cloning and hormonal regulation of PiT-1, a sodium-dependent phosphate cotransporter from rat parathyroid glands. Endocrinology 87 9528951
2010 The phosphate transporter PiT1 (Slc20a1) revealed as a new essential gene for mouse liver development. PloS one 86 20161774
1992 An alternatively spliced Pit-1 isoform altered in its ability to trans-activate. Nucleic acids research 82 1561093
2005 Novel mutations within the POU1F1 gene associated with variable combined pituitary hormone deficiency. The Journal of clinical endocrinology and metabolism 80 15928241
2009 PROP1 coexists with SOX2 and induces PIT1-commitment cells. Biochemical and biophysical research communications 74 19442651
1994 Multiple Pit-1-binding sites facilitate estrogen responsiveness of the prolactin gene. Molecular endocrinology (Baltimore, Md.) 73 7708061
1991 Thyrotropin-releasing hormone action on the prolactin promoter is mediated by the POU protein pit-1. Molecular endocrinology (Baltimore, Md.) 70 1922085
1993 A thyrotrope-specific variant of Pit-1 transactivates the thyrotropin beta promoter. The Journal of biological chemistry 64 8407911
1995 A novel E250X mutation of the PIT1 gene in a patient with combined pituitary hormone deficiency. Endocrine journal 59 7670563
1998 RNA levels of human retrovirus receptors Pit1 and Pit2 do not correlate with infectibility by three retroviral vector pseudotypes. Human gene therapy 56 9853528
1998 Rarity of PIT1 involvement in children from Russia with combined pituitary hormone deficiency. American journal of medical genetics 48 9632165
2010 Deregulation of the Pit-1 transcription factor in human breast cancer cells promotes tumor growth and metastasis. The Journal of clinical investigation 46 21060149
1999 Subnuclear partitioning and functional regulation of the Pit-1 transcription factor. Journal of cellular biochemistry 44 10022514
1993 Analysis of Pit-1 in regulating mouse TSH beta promoter activity in thyrotropes. Molecular and cellular endocrinology 44 8276142
1996 Pit-1: clinical aspects. Hormone research 43 8805025
2009 Generation of mouse conditional and null alleles of the type III sodium-dependent phosphate cotransporter PiT-1. Genesis (New York, N.Y. : 2000) 42 19882669
2004 Regulation of phosphate (Pi) transport and NaPi-III transporter (Pit-1) mRNA in rat osteoblasts. The Journal of endocrinology 42 15171701
2021 POU1F1 transcription factor induces metabolic reprogramming and breast cancer progression via LDHA regulation. Oncogene 41 33714987
2005 Functional relationship between LHX4 and POU1F1 in light of the LHX4 mutation identified in patients with pituitary defects. The Journal of clinical endocrinology and metabolism 41 15998782
1992 Activin inhibits binding of transcription factor Pit-1 to the growth hormone promoter. Proceedings of the National Academy of Sciences of the United States of America 40 1454833
2001 Combined pituitary hormone deficiency caused by compound heterozygosity for two novel mutations in the POU domain of the Pit1/POU1F1 gene. The Journal of clinical endocrinology and metabolism 39 11297581
2012 NELL-1 increases pre-osteoblast mineralization using both phosphate transporter Pit1 and Pit2. Biochemical and biophysical research communications 38 22580275
2021 High-throughput splicing assays identify missense and silent splice-disruptive POU1F1 variants underlying pituitary hormone deficiency. American journal of human genetics 35 34270938
1995 Pituitary-type transcription of the human prolactin gene in the absence of Pit-1. Molecular endocrinology (Baltimore, Md.) 35 7476971
2000 Pituitary and extrapituitary growth hormone: Pit-1 dependence? Canadian journal of physiology and pharmacology 34 11149379
1993 Promoter activity of human renin 5'-flanking DNA sequences is activated by the pituitary-specific transcription factor Pit-1. The Journal of biological chemistry 34 8420924
2019 POU1F1 transcription factor promotes breast cancer metastasis via recruitment and polarization of macrophages. The Journal of pathology 33 31292963
2002 Reassessing the role of region A in Pit1-mediated viral entry. Journal of virology 33 12097582
2005 Role of prophet of Pit1 (PROP1) in gonadotrope differentiation and puberty. Endocrinology 31 16384867
2018 PiT1/Slc20a1 Is Required for Endoplasmic Reticulum Homeostasis, Chondrocyte Survival, and Skeletal Development. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 30 30347511
2015 Functional characterization of a human POU1F1 mutation associated with isolated growth hormone deficiency: a novel etiology for IGHD. Human molecular genetics 30 26612202
2019 Novel function of PiT1/SLC20A1 in LPS-related inflammation and wound healing. Scientific reports 28 30755642
2016 Calcium Overload Accelerates Phosphate-Induced Vascular Calcification Via Pit-1, but not the Calcium-Sensing Receptor. Journal of atherosclerosis and thrombosis 28 27840385
2008 Functions of PIT1 in GATA2-dependent transactivation of the thyrotropin beta promoter. Journal of molecular endocrinology 28 19103719
2002 Domains of Pit-1 required for transcriptional synergy with GATA-2 on the TSH beta gene. Molecular and cellular endocrinology 28 12385825
2023 Multilineage Pituitary Neuroendocrine Tumors (PitNETs) Expressing PIT1 and SF1. Endocrine pathology 27 37268858
1998 Expression of the tissue-specific transcription factor Pit-1 in the lancelet, Branchiostoma lanceolatum. The Journal of comparative neurology 27 9511922
2009 Effects of transgenic Pit-1 overexpression on calcium phosphate and bone metabolism. Journal of bone and mineral metabolism 26 19795094
1996 In situ hybridization analysis of Pit-1 mRNA and hormonal production in human pituitary adenomas. Acta neuropathologica 26 8834538
1995 In vivo mutational analysis of the DNA binding domain of the tissue-specific transcription factor, Pit-1. The Journal of biological chemistry 26 7592721
2005 Association of PIT1, GH and GHRH polymorphisms with performance and carcass traits in Landrace pigs. Journal of applied genetics 24 15876687
2004 Immunolocalization of Pit-1 in gonadotroph nuclei is indicative of the transdifferentiation of gonadotroph to lactotroph cells in prolactinomas induced by estrogen. Histochemistry and cell biology 24 15221415
2014 Molecular analysis of PROP1, POU1F1, LHX3, and HESX1 in Turkish patients with combined pituitary hormone deficiency: a multicenter study. Endocrine 22 25500790
2005 Absent or delayed adrenarche in Pit-1/POU1F1 deficiency. Hormone research 22 16210857
1996 Thyroid hormone receptor beta2 promoter activity in pituitary cells is regulated by Pit-1. The Journal of biological chemistry 22 8798664
1995 A dopamine-responsive domain in the N-terminal sequence of Pit-1. Transcriptional inhibition in endocrine cell types. The Journal of biological chemistry 22 7706253
2020 Slc20a1/Pit1 and Slc20a2/Pit2 are essential for normal skeletal myofiber function and survival. Scientific reports 21 32080237
2013 ox-LDL induces PiT-1 expression in human aortic valve interstitial cells. The Journal of surgical research 21 23849774
2008 The PIT1 gene polymorphisms were associated with chicken growth traits. BMC genetics 21 18304318
2002 Neonatal Meishan pigs show POU1F1 genotype effects on plasma GH and PRL concentration. Animal reproduction science 21 11812632
2017 Magnesium prevents phosphate-induced vascular calcification via TRPM7 and Pit-1 in an aortic tissue culture model. Hypertension research : official journal of the Japanese Society of Hypertension 20 28123180
2016 A Sex-Dependent, Tropic Role for Leptin in the Somatotrope as a Regulator of POU1F1 and POU1F1-Dependent Hormones. Endocrinology 20 27571135
2003 The de novo Q167K mutation in the POU1F1 gene leads to combined pituitary hormone deficiency in an Italian patient. Pediatric research 20 12904605
2002 A novel mutation in PIT-1: phenotypic variability in familial combined pituitary hormone deficiencies. Journal of pediatric endocrinology & metabolism : JPEM 20 11924936
1993 Pit-1 and pituitary function. The Journal of pediatric endocrinology 20 7920987
2021 PD-L1 Is Preferentially Expressed in PIT-1 Positive Pituitary Neuroendocrine Tumours. Endocrine pathology 19 33694064
2021 Phosphate Overload Stimulates Inflammatory Reaction via PiT-1 and Induces Vascular Calcification in Uremia. Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation 19 34688540
2004 A new single nucleotide polymorphism in the chicken pituitary-specific transcription factor (POU1F1) gene associated with growth rate. Animal genetics 19 15265078
2000 Biochemical and genetic characterization of the porcine Prophet of Pit-1 pituitary transcription factor. Molecular and cellular endocrinology 19 11064154
2016 Identification of Novel PROP1 and POU1F1 Mutations in Patients with Combined Pituitary Hormone Deficiency. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 18 27756091
2005 The role of CBP/p300 interactions and Pit-1 dimerization in the pathophysiological mechanism of combined pituitary hormone deficiency. The Journal of clinical endocrinology and metabolism 18 16263824
2002 Lack of association of GH1 and POU1F1 gene variants with meat production traits in Piemontese cattle. Animal genetics 18 11849139
1995 Activin increases phosphorylation and decreases stability of the transcription factor Pit-1 in MtTW15 somatotrope cells. The Journal of biological chemistry 18 7499395
2019 Spironolactone dose‑dependently alleviates the calcification of aortic rings cultured in hyperphosphatemic medium with or without hyperglycemia by suppressing phenotypic transition of VSMCs through downregulation of Pit‑1. Molecular medicine reports 17 30896801
2014 Cancer progression by breast tumors with Pit-1-overexpression is blocked by inhibition of metalloproteinase (MMP)-13. Breast cancer research : BCR 17 25527274
2007 A novel germline mutation, IVS4+1G>A, of the POU1F1 gene underlying combined pituitary hormone deficiency. Hormone research 17 18059085
2005 EGF stimulates Pit-1 independent transcription of the human prolactin pituitary promoter in human breast cancer SK-BR-3 cells through its proximal AP-1 response element. Molecular and cellular endocrinology 17 15607537
1996 The ontogeny of pit-1 expression in the human fetal pituitary gland. Neuroendocrinology 17 8739890
1995 Screening for PIT1 abnormality by PCR direct sequencing method. Thyroid : official journal of the American Thyroid Association 17 7580269
2008 A PstI polymorphism at 3'UTR of goat POU1F1 gene and its effect on cashmere production. Molecular biology reports 16 18654839
2006 Effect of genetic variations of the POU1F1 gene on growth traits of Nanyang cattle. Yi chuan xue bao = Acta genetica Sinica 16 17046590
1998 Synthesis of turkey Pit-1 mRNA variants by alternative splicing and transcription initiation. DNA and cell biology 16 9468226
1998 Clinical and molecular characterization of a Brazilian patient with Pit-1 deficiency. Journal of pediatric endocrinology & metabolism : JPEM 16 9829213
1998 Retrovirus receptor PiT-1 of the Felis catus. Biochimica et biophysica acta 16 9878855
1996 Immunocytochemical localization of the Pit-1 protein in the pituitary of the rainbow trout (Oncorhynchus mykiss). General and comparative endocrinology 16 8860305
1995 Pit-1 exhibits a unique promoter spacing requirement for activation and synergism. The Journal of biological chemistry 16 7876215
2016 A novel heterozygous intronic mutation in POU1F1 is associated with combined pituitary hormone deficiency. Endocrine journal 15 27885216
2014 Loss of PiT-1 results in abnormal endocytosis in the yolk sac visceral endoderm. Mechanisms of development 15 25138534
2012 Analysis of polymorphism within POU1F1 gene in relation to milk production traits in dairy Sarda sheep breed. Molecular biology reports 15 22311029
1998 Molecular cloning of pit-1 cDNA from porcine anterior pituitary and its involvement in pituitary stimulation by growth hormone-releasing factor. Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association 15 9710361