Affinage

PTF1A

Pancreas transcription factor 1 subunit alpha · UniProt Q7RTS3

Length
328 aa
Mass
35.0 kDa
Annotated
2026-04-28
100 papers in source corpus 32 papers cited in narrative 32 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PTF1A is a tissue-restricted basic helix-loop-helix transcription factor that functions as the DNA-binding subunit of the trimeric PTF1 complex (with an E-protein and RBPJ/RBPJL), serving as a master regulator of cell fate specification in the pancreas, cerebellum, spinal cord, and retina (PMID:8861960, PMID:11318877). In the pancreas, PTF1A specifies multipotent progenitor identity—its loss redirects progenitors to intestinal fates—and continuously maintains acinar cell differentiation by directly activating digestive enzyme genes, Pdx1, Mnx1, and Dll1 while cross-repressing endocrine programs antagonized by Nkx6 factors; loss of PTF1A in adult acinar cells induces metaplasia and potentiates KRAS-driven neoplasia (PMID:12185368, PMID:20627083, PMID:27697859, PMID:26151762). In neural tissues, PTF1A specifies GABAergic/inhibitory neuronal fates over glutamatergic fates through downstream effectors including Prdm13, Tfap2a/b, and Pax2, with tissue-specific target selection governed by lineage-restricted chromatin accessibility and cofactors such as Foxa2 (PMID:16039563, PMID:16291784, PMID:24370451, PMID:23754747). Loss-of-function mutations in human PTF1A cause pancreatic and cerebellar agenesis (PMID:15543146).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1996 High

    Identification of PTF1A/p48 as the cell-type-specific bHLH subunit of the PTF1 complex resolved how pancreas-restricted DNA-binding activity is conferred, establishing the molecular identity of the complex's specificity determinant.

    Evidence cDNA cloning, bHLH domain analysis, and correlation of p48 expression with PTF1 DNA-binding activity across cell types

    PMID:8861960

    Open questions at the time
    • Stoichiometry and structure of the full PTF1 complex not yet determined
    • Identity of the other PTF1 subunits not fully characterized at this stage
  2. 1998 High

    Demonstrating that Ptf1a-null mice completely lack exocrine pancreas while endocrine cells persist (mis-localized) established PTF1A as an essential and selective determinant of the exocrine lineage.

    Evidence Ptf1a-null mouse knockout with histological and molecular phenotyping

    PMID:9851981

    Open questions at the time
    • Whether Ptf1a acts in multipotent progenitors or committed exocrine precursors was unresolved
    • Mechanism of endocrine cell mis-localization not explained
  3. 2001 High

    Discovery that PTF1A physically binds RBPJ (the Notch pathway effector) and that RBPJ stimulates PTF1A/E47-dependent transcription defined the trimeric composition of the PTF1 complex and revealed a Notch-independent role for RBPJ.

    Evidence Yeast two-hybrid, co-immunoprecipitation, and transcriptional reporter assays

    PMID:11318877

    Open questions at the time
    • Whether the PTF1A–RBPJ interaction competes with Notch for RBPJ binding in vivo was not resolved
    • Structural basis of the PTF1A–RBPJ interaction unknown
  4. 2002 High

    Lineage tracing showed Ptf1a marks multipotent pancreatic progenitors (not just exocrine cells), and its loss redirects these progenitors to intestinal fate, redefining PTF1A as a pancreatic organ identity factor rather than an exocrine-restricted gene.

    Evidence Recombination-based lineage tracing in Ptf1a-null mice plus Pdx1 transgene rescue

    PMID:12185368

    Open questions at the time
    • Signals upstream of Ptf1a that initiate its expression in progenitors were not identified
  5. 2004 High

    Human loss-of-function mutations in PTF1A causing pancreatic and cerebellar agenesis established PTF1A as essential for both organs in humans and identified a functionally critical C-terminal domain beyond the bHLH region.

    Evidence Positional cloning of human mutations (705insG, C886T), reporter assays with deletion mutants, Ptf1a-null mouse neuropathology

    PMID:15543146

    Open questions at the time
    • Molecular function of the C-terminal domain (later shown as RBPJ-binding) was not fully defined
    • Extent of cerebellar versus brainstem phenotype in humans not fully characterized
  6. 2005 High

    Demonstrating that Ptf1a specifies GABAergic over glutamatergic neuronal fate in both cerebellum and spinal cord—with fate switches to excitatory neurons upon loss—established a conserved role for PTF1A as a binary inhibitory/excitatory fate switch across the CNS.

    Evidence Ptf1a-null mouse analysis in cerebellum (cerebelless mutant) and spinal cord with lineage tracing and ectopic expression

    PMID:16039563 PMID:16291784

    Open questions at the time
    • Direct transcriptional targets mediating the GABAergic fate choice were unknown
    • Whether PTF1A actively represses glutamatergic genes or only activates GABAergic programs was unclear
  7. 2007 High

    Extension of PTF1A's neuronal fate-specification role to the retina (horizontal and amacrine cells) and inferior olive (climbing fiber neurons) demonstrated that PTF1A operates as a GABAergic/inhibitory cell fate determinant across all major CNS regions where it is expressed.

    Evidence Lineage tracing and conditional inactivation in retina; Ptf1a-null analysis in hindbrain with retrograde labeling

    PMID:17075007 PMID:17301087 PMID:17928434

    Open questions at the time
    • Downstream transcriptional programs in retina and hindbrain not yet mapped
    • Ptf1a's role in olivary neuron migration versus specification not fully distinguished
  8. 2007 High

    Showing that Ptf1a directly occupies and activates the Pdx1 area III enhancer in embryonic pancreas via a PTF1-binding site established the first direct transcriptional target linking PTF1A to progenitor gene regulation.

    Evidence ChIP from E11.5 pancreatic buds, transgenic reporter assays with site mutagenesis

    PMID:17403901

    Open questions at the time
    • Genome-wide target repertoire not yet known
    • Whether Ptf1a activates Pdx1 in neural tissues was not tested
  9. 2008 High

    Identification of PTF1A autoregulatory loops (via its own 2.3-kb enhancer containing PTF1-binding sites) and a Ptf1a→Dll1→Hes1→Ptf1a feed-forward circuit revealed how PTF1A expression is sustained in pancreatic progenitors.

    Evidence Transgenic reporters with site-directed mutagenesis, ChIP, and genetic epistasis with Dll1/Hes1 mutants

    PMID:18606784 PMID:22096075

    Open questions at the time
    • Whether the autoregulatory loop is active in neural progenitors was unknown at this point
    • Quantitative dynamics of the feed-forward loop not modeled
  10. 2009 High

    Demonstrating that the PTF1-J complex (Ptf1a/E-protein/Rbpj) directly activates Neurog2 in dorsal spinal cord via a 3' enhancer—and autoregulates Ptf1a in neural tissue—identified the first direct neural target and showed the same trimeric complex operates in both pancreas and nervous system.

    Evidence ChIP from neural tube, enhancer mutagenesis, transgenic reporters, and Ptf1a gain/loss of function in mouse and chick

    PMID:19641016 PMID:19741120

    Open questions at the time
    • Full neural target gene repertoire not determined
    • Whether RBPJL substitutes for RBPJ in any neural context was untested
  11. 2010 High

    Establishing that Nkx6 factors and Ptf1a act as mutual cross-repressive lineage determinants in pancreatic progenitors explained how the endocrine-versus-acinar binary fate decision is enforced.

    Evidence Reciprocal genetic loss- and gain-of-function in mouse with lineage marker analysis

    PMID:20627083

    Open questions at the time
    • Whether the cross-repression is direct (PTF1A binding Nkx6 loci and vice versa) was not resolved
    • Chromatin-level mechanism of repression not characterized
  12. 2012 High

    Genome-wide ChIP-seq in pancreatic progenitors mapped PTF1A's direct target repertoire, revealing regulation of Mnx1, Pdx1, Nkx6.1, and Onecut1 through distal enhancers and defining a transcription factor network for progenitor maintenance.

    Evidence ChIP-seq combined with RNA profiling in pancreas progenitors

    PMID:22232429

    Open questions at the time
    • Functional validation of most enhancer targets was lacking
    • Dynamic changes in PTF1A binding during differentiation not captured
  13. 2013 High

    Comparative ChIP-seq in pancreas versus neural tube revealed that tissue-specific PTF1A binding is determined by pre-existing chromatin accessibility and lineage cofactors (Foxa2 in pancreas; Sox factors in neural tissue), explaining how one transcription factor drives different programs in different tissues.

    Evidence ChIP-seq in pancreas and neural tube, chromatin accessibility analysis, cotransfection assays with Foxa2

    PMID:23754747

    Open questions at the time
    • Identity of the neural-specific cofactors (Sox family members) not functionally validated
    • Causal relationship between cofactor binding and PTF1A recruitment not established
  14. 2013 High

    Identification of Prdm13 as a direct PTF1A–RBPJ target that suppresses glutamatergic fate by blocking Neurog2-mediated Tlx3 activation provided the first downstream effector mechanism for PTF1A's inhibitory neuron specification.

    Evidence Gain/loss-of-function in Xenopus and chick neural tube, Ptf1a-null mouse, molecular epistasis

    PMID:24370451

    Open questions at the time
    • Whether Prdm13 is sufficient to fully recapitulate Ptf1a's GABAergic specification was not shown
    • Prdm13 enzymatic substrates not identified
  15. 2015 High

    Discovery that PTF1A loss induces acinar-to-ductal metaplasia and synergizes with oncogenic KRAS to drive pancreatic neoplasia established PTF1A as a tumor suppressor that actively maintains differentiated acinar identity.

    Evidence Conditional Ptf1a KO combined with oncogenic KRAS, acinar lineage tracing, expression profiling in mouse

    PMID:26151762

    Open questions at the time
    • Whether PTF1A re-expression can reverse established metaplasia or neoplasia was not tested
    • Mechanism by which PTF1A loss cooperates with KRAS at the chromatin level unknown
  16. 2016 High

    Comprehensive ChIP-seq and RNA-seq in adult mice showed PTF1A directly controls digestive enzyme genes, UPR components, and a ten-member transcription factor network in mature acinar cells, defining its continuous role in maintaining the differentiated secretory phenotype.

    Evidence Conditional PTF1A depletion in adult mice with transcriptome and ChIP-seq analysis

    PMID:27697859

    Open questions at the time
    • How PTF1A coordinates UPR with secretory function at the mechanistic level is unclear
    • Epigenetic changes following PTF1A loss in adult acinar cells not fully characterized
  17. 2018 High

    Demonstrating that Ptf1a alone can reprogram fibroblasts into induced neural stem cells—dependent on its RBPJ interaction domain—showed that PTF1A's partnership with RBPJ is sufficient to activate a self-renewing neural progenitor program.

    Evidence Direct reprogramming of mouse and human fibroblasts, RBPJ-interaction domain mutagenesis, NSC marker and Notch pathway analysis

    PMID:30030434

    Open questions at the time
    • In vivo relevance of PTF1A-driven reprogramming not tested
    • Whether reprogrammed NSCs have full differentiation potential comparable to endogenous NSCs is unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the structural basis of the PTF1A–RBPJ–E-protein trimeric complex, how PTF1A mechanistically switches between activator and repressor modes at different genomic loci, the identity and functional validation of neural-specific cofactors, and whether PTF1A restoration can reverse acinar metaplasia or pancreatic neoplasia.
  • No crystal or cryo-EM structure of the PTF1 trimeric complex
  • Mechanism of PTF1A-mediated transcriptional repression (e.g., at Nkx6, Atoh7 loci) not characterized
  • Neural-specific cofactors functionally unvalidated

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 5
Pathway
R-HSA-1266738 Developmental Biology 11 R-HSA-162582 Signal Transduction 3
Partners
ATOH1FOXA2NKX6-1PDX1PRDM13RBPJRBPJLTCF3
Complex memberships
PTF1 complex (PTF1A/E-protein/RBPJ)PTF1-L complex (PTF1A/E-protein/RBPJL)

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 PTF1A (p48) is the cell-specific DNA-binding bHLH subunit of the heterooligomeric transcription factor PTF1; its pancreas-restricted synthesis confers cell-specific DNA-binding activity to the PTF1 complex. cDNA cloning, bHLH domain sequence analysis, correlation of p48 expression with PTF1 DNA-binding activity in pancreatic vs. non-pancreatic cells The EMBO journal High 8861960
1998 PTF1A/p48 is required for differentiation and/or proliferation of the exocrine pancreatic cell lineage; null mutation causes complete absence of exocrine pancreatic tissue while endocrine cells are present but mis-localized to the spleen. Mouse knockout (null allele generation), histological and molecular analysis of exocrine and endocrine lineages in Ptf1a-null mice Genes & development High 9851981
2002 Ptf1a is expressed in multipotent pancreatic progenitors (not exclusively exocrine cells); inactivation of Ptf1a causes pancreatic progenitors to adopt intestinal/duodenal epithelial fates, demonstrating Ptf1a specifies pancreatic progenitor identity. Recombination-based lineage tracing in vivo, Ptf1a-null mice phenotypic analysis, Ptf1a cis-regulatory sequence-driven Pdx1 transgene rescue Nature genetics High 12185368
2004 Loss-of-function mutations in PTF1A (705insG and C886T causing C-terminal truncation) cause pancreatic and cerebellar agenesis in humans; a C-terminal domain beyond the bHLH region is essential for PTF1A function as shown by reporter-gene studies. Positional cloning, mutation identification, reporter-gene assays with PTF1A deletion mutants, neuropathological analysis of Ptf1a-null mice Nature genetics High 15543146
2004 Aortal endothelial cells induce expression of Ptf1a in the dorsal pancreatic endoderm; this induction is specific to dorsal pancreas development and is mediated by the aorta cells themselves independent of blood supply. Flk1-/- mouse embryos lacking endothelial cells, tissue recombination experiments, explant co-culture assays Development (Cambridge, England) High 14736742
2005 Ptf1a is required in cerebellar ventricular zone progenitors to specify GABAergic neuronal fate; in its absence, progenitors produce glutamatergic neurons instead, causing loss of the entire cerebellar cortex. Genetic identification of cerebelless mutant, lineage tracing of Ptf1a-expressing progenitors, ectopic Ptf1a introduction into dorsal telencephalon glutamatergic progenitors Neuron High 16039563
2005 Ptf1a is required for GABAergic over glutamatergic neuronal fate in the spinal cord dorsal horn; its null mutation causes dI4 interneurons to trans-fate to dI5 (Lmx1b+) and dILA to dILB (Lmx1b+;Tlx3+), resulting in complete loss of inhibitory GABAergic neurons. Ptf1a null mouse analysis, homeodomain factor marker analysis (Lhx1/5, Pax2, Lmx1b, Tlx3) at defined developmental stages Development (Cambridge, England) High 16291784
2006 Ptf1a determines horizontal and amacrine cell fates in the mouse retina; inactivation of Ptf1a causes fate-switch of these precursors to ganglion cells, with complete loss of horizontal cells and profound decrease of amacrine cells. Recombination-based lineage tracing, Ptf1a conditional inactivation in retina, cell-type marker analysis Development (Cambridge, England) High 17075007
2001 PTF1A/p48 physically binds to RBP-Jkappa (the intracellular Notch signaling mediator); p48 binds RBP-Jkappa more strongly and in a distinct manner from Notch1. The p48/E47-activated transcription from the PTF1 motif is further stimulated by RBP-Jkappa. Yeast two-hybrid binding assay, co-immunoprecipitation, transcriptional reporter assays in cell lines, Xenopus overexpression Genes to cells : devoted to molecular & cellular mechanisms High 11318877
2008 PTF1a transcriptional autoregulation is mediated by a 2.3-kb enhancer containing two evolutionarily conserved binding sites for the active trimeric PTF1 complex (PTF1a/E-protein/RBPJ or RBPJL); the two PTF1 sites are essential for acinar cell-specific transcription, establishing an autoregulatory loop. Transgenic mouse reporter assays, transfection in cell lines, site-directed mutagenesis of PTF1 binding sites, chromatin immunoprecipitation (ChIP) Molecular and cellular biology High 18606784
2010 Nkx6 transcription factors and Ptf1a function as cross-repressive antagonistic lineage determinants in multipotent pancreatic progenitors; Nkx6 factors and Ptf1a are each required and sufficient to repress the alternative lineage program and specify progenitors toward endocrine or acinar fate respectively. Genetic loss- and gain-of-function approaches in mouse, cell lineage marker analysis Developmental cell High 20627083
2007 Ptf1a directly binds to and activates area III of the Pdx1 promoter via a PTF1 binding site; Ptf1a occupies this genomic region in E11.5 pancreatic buds and drives early pancreas-wide Pdx1 expression. Cre-mediated lineage tracing, transgenic reporter assays, transfection assays, chromatin immunoprecipitation from embryonic pancreatic tissue Molecular and cellular biology High 17403901
2009 The PTF1-J complex (Ptf1a/E-protein/Rbpj trimer) directly activates Neurog2 transcription in dorsal spinal cord through a 3' enhancer containing a PTF1-J binding site; Ptf1a occupies this enhancer in vivo (ChIP from neural tube tissue), and Ptf1a gain and loss of function alter Neurog2 enhancer activity. Enhancer identification and mutagenesis, in vivo transgenic reporter assays in mouse and chick, Ptf1a gain/loss of function, chromatin immunoprecipitation from neural tube Development (Cambridge, England) High 19641016
2009 PTF1-J complex autoregulates Ptf1a expression in the nervous system through a conserved 5' 2.3-kb regulatory element; Ptf1a localizes to this genomic region in vivo (ChIP) and is required for the element's activity in transgenic mice. Transgenic mouse reporter assays, in vitro PTF1-J binding assays, ChIP from neural tissue, Ptf1a-dependent in vivo reporter activity The Journal of neuroscience : the official journal of the Society for Neuroscience High 19741120
2008 Ptf1a directly activates Dll1 expression in multipotent pancreatic progenitor cells; Ptf1a-induced Dll1 activates Hes1, which in turn is required to sustain Ptf1a expression, forming a regulatory loop that maintains progenitor proliferation. Genetic epistasis analysis with Dll1, Hes1, and Ptf1a mutant mice; proliferation analysis of multipotent progenitor cells Development (Cambridge, England) High 22096075
2008 Ptf1a is required for glycinergic and peptidergic neurotransmitter phenotypes in dorsal spinal inhibitory neurons in addition to GABA; Ptf1a is a master regulator upstream of Pax2 (a downstream target) and Lbx1, controlling multiple neurotransmitter phenotypes. Ptf1a null mouse analysis, marker gene expression analysis for GlyT2, NPY, N/OFQ, SOM, ENK, DYN, GAL; genetic epistasis with Pax2 and Lbx1 mutants Developmental biology High 18634777
2012 PTF1a directly regulates Mnx1 through a distant enhancer element in pancreatic progenitors; PTF1a also directly promotes expression of Pdx1, Nkx6.1, and Onecut1, forming a transcription factor network for progenitor maintenance. RNA profiling combined with ChIP-sequencing in pancreas progenitors Molecular and cellular biology High 22232429
2013 Ptf1a binding specificity in pancreas vs. neural tube is determined by distinct chromatin accessibility landscapes and lineage-specific cofactors; Foxa2 co-localizes with Ptf1a in embryonic pancreatic chromatin and acts synergistically with Ptf1a in transcriptional activation; Sox factors are enriched as potential neural cofactors. ChIP-seq in pancreas and neural tube tissue, transgenic reporter assays, cotransfection assays with Foxa2, chromatin accessibility analysis Molecular and cellular biology High 23754747
2013 Prdm13 histone methyltransferase is a direct transcriptional target of the Ptf1a-Rbpj complex in dorsal spinal cord; Prdm13 suppresses glutamatergic (Tlx3+) and promotes GABAergic (Pax2+) neuronal fate by blocking Neurog2-mediated Tlx3 activation. Gain/loss-of-function in Xenopus and chick neural tube, Ptf1a-/- mouse analysis, molecular epistasis between Prdm13 and Neurog2/Tlx3 Developmental biology High 24370451
2015 PTF1A expression is lost in pancreatic intraepithelial neoplasia (PanIN) and is functionally required to suppress acinar reprogramming; loss of Ptf1a alone is sufficient to induce acinar-to-ductal metaplasia and potentiate oncogenic KRAS transformation, identifying PTF1A as a tumor suppressor in the pancreas. Mouse genetics (Ptf1a conditional KO with oncogenic KRAS), acinar cell lineage tracing, gene expression profiling eLife High 26151762
2016 PTF1A maintains adult pancreatic acinar cell identity by directly controlling genes for secretory digestive enzyme production, unfolded protein response, and an interconnected ten-member transcription factor network; its depletion causes UPR imbalance, cellular injury, and acinar metaplasia with derepression of stomach-characteristic genes. Conditional PTF1A depletion in adult mice, transcriptome sequencing, chromatin immunoprecipitation sequencing (ChIP-seq) Molecular and cellular biology High 27697859
2004 PTF1A inhibits proliferation of acinar and non-acinar cells by upregulating p21CIP1/WAF1 and p27KIP1 and downregulating cyclin D2, causing G1-S delay; these antiproliferative effects depend on the C-terminal region of p48 and do not require the bHLH domain. Transfection of p48 cDNA and deletion mutants into pancreatic and nonpancreatic cells, cell cycle analysis, Western blotting, promoter reporter assays Gastroenterology Medium 15362048
2007 Ptf1a specifies GABAergic amacrine and horizontal cell fates in the retina; within the Ptf1a-expressing lineage, GABAergic and glycinergic amacrine cells and horizontal cells are completely absent in Ptf1a-knockout retinas while a small population of non-GABAergic/non-glycinergic amacrine cells persists. Lineage tracing, Ptf1a knockout retinal explant analysis, cell-type specific marker immunostaining Development (Cambridge, England) High 17301087
2007 Ptf1a is required for the development of climbing fiber neurons in the inferior olivary nucleus; in Ptf1a null mice, climbing fiber neuron progenitors from the Ptf1a domain cannot migrate or differentiate, fail to form the inferior olivary nucleus, and some cells are redirected to mossy fiber neuron fate. Beta-galactosidase lineage tracing from Ptf1a locus, retrograde labeling, Ptf1a null mutant analysis, apoptosis and migration studies The Journal of neuroscience : the official journal of the Society for Neuroscience High 17928434
2014 In the absence of Ptf1a, cerebellar ventricular zone cells initiate a more ventral brainstem expression program (LIM homeobox transcription factor 1 beta and T-cell leukemia homeobox 3), exit the cerebellar anlage, and contribute to adjacent brainstem or die, causing cerebellar agenesis. Genetic fate mapping in Ptf1a-/- mice, gene expression analysis of cell fate markers Proceedings of the National Academy of Sciences of the United States of America High 24733890
2008 Pdx-1 is required in the foregut endoderm prior to Ptf1a for pancreatic MPC specification; Ptf1a is neither required for specification of Ngn3-positive endocrine progenitors nor for differentiation of mature beta-cells, while Pdx-1 loss precludes sustained Ngn3-based endocrine progenitor derivation. Double Pdx-1;Ptf1a null mouse analysis, novel Ptf1aYFP allele lineage tracing, cell marker analysis Developmental biology High 18294628
2018 Ptf1a alone is sufficient to directly reprogram mouse and human fibroblasts into induced neural stem cells; this reprogramming depends on Ptf1a's Notch-independent interaction with Rbpj, which activates transcription factor genes and Notch signaling required for NSC specification and self-renewal. Direct reprogramming assays, Rbpj interaction domain mutagenesis, gene expression analysis of NSC markers and Notch pathway components Nature communications High 30030434
2013 Ptf1a and Atoh1 specify spatial identities of cerebellar neuron progenitors (GABAergic and glutamatergic, respectively) and mutually negatively regulate each other's expression to maintain non-overlapping neuroepithelial domains. Knock-in mouse lines (Ptf1aAtoh1 and Atoh1Ptf1a), in utero electroporation, BrdU birthdating, marker analysis The Journal of neuroscience : the official journal of the Society for Neuroscience High 24695699
2015 Tfap2a and Tfap2b are major downstream effectors of Ptf1a in retinal amacrine cell differentiation; their expression is dramatically downregulated in Ptf1a-null retina; their overexpression promotes glycinergic and GABAergic amacrine cell differentiation similar to Ptf1a misexpression, defining a Foxn4/RORβ1-Ptf1a-Tfap2a/2b transcriptional cascade. RNA-seq of Ptf1a null retina, immunolabeling, overexpression and knockdown experiments in mouse retina Molecular brain High 25966682
2011 Ptf1a/Rbpj complex is required to inhibit ganglion cell fate and drive specification of all horizontal cell subtypes in chick retina; the Rbpj-interacting domains of Ptf1a are required for its cell fate specification effects, and Ptf1a strongly represses Atoh7 expression. Retrovirus-mediated gene transfer in chick retina, Ptf1a domain mutagenesis (Rbpj-interacting domain deletion), cell-type marker analysis Developmental biology Medium 21839069
2006 Combined ectopic expression of XPtf1a/p48 and XlHbox8 (Pdx1) in Xenopus converts posterior endoderm into both endocrine and exocrine pancreatic tissue; Ptf1a alone expands the pancreatic territory only within the borders of XlHbox8 expression. Ectopic mRNA injection in Xenopus embryos, pan-endodermal and transthyretin-promoter-driven transgene expression, morphological and marker analysis Genes & development Medium 16751182
2011 Postembryonic antagonism of Ptf1a induces acinar-to-endocrine conversion in zebrafish; lineage tracing confirms that induced insulin+ cells are derived from acinar cells, indicating Ptf1a continuously maintains acinar cell fate and represses endocrine differentiation. Postembryonic Ptf1a antagonism, genetic lineage tracing of acinar cells in zebrafish Current biology : CB High 21497092

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 The role of the transcriptional regulator Ptf1a in converting intestinal to pancreatic progenitors. Nature genetics 805 12185368
1999 Expression of the p48 xeroderma pigmentosum gene is p53-dependent and is involved in global genomic repair. Proceedings of the National Academy of Sciences of the United States of America 477 9892649
1998 The bHLH protein PTF1-p48 is essential for the formation of the exocrine and the correct spatial organization of the endocrine pancreas. Genes & development 416 9851981
2005 Ptf1a, a bHLH transcriptional gene, defines GABAergic neuronal fates in cerebellum. Neuron 382 16039563
2001 A central role for P48/45 in malaria parasite male gamete fertility. Cell 338 11163248
2004 Mutations in PTF1A cause pancreatic and cerebellar agenesis. Nature genetics 310 15543146
2000 Xeroderma pigmentosum p48 gene enhances global genomic repair and suppresses UV-induced mutagenesis. Molecular cell 271 10882109
2013 Spatiotemporal patterns of multipotentiality in Ptf1a-expressing cells during pancreas organogenesis and injury-induced facultative restoration. Development (Cambridge, England) 239 23325761
2010 Nkx6 transcription factors and Ptf1a function as antagonistic lineage determinants in multipotent pancreatic progenitors. Developmental cell 220 20627083
1997 Interferon-resistant human melanoma cells are deficient in ISGF3 components, STAT1, STAT2, and p48-ISGF3gamma. The Journal of biological chemistry 214 9353349
2013 Recessive mutations in a distal PTF1A enhancer cause isolated pancreatic agenesis. Nature genetics 208 24212882
1996 Essential and non-redundant roles of p48 (ISGF3 gamma) and IRF-1 in both type I and type II interferon responses, as revealed by gene targeting studies. Genes to cells : devoted to molecular & cellular mechanisms 206 9078371
2006 Ptf1a determines horizontal and amacrine cell fates during mouse retinal development. Development (Cambridge, England) 199 17075007
2004 Endothelial cell interactions initiate dorsal pancreas development by selectively inducing the transcription factor Ptf1a. Development (Cambridge, England) 193 14736742
1996 The p48 DNA-binding subunit of transcription factor PTF1 is a new exocrine pancreas-specific basic helix-loop-helix protein. The EMBO journal 186 8861960
2005 Ptf1a determines GABAergic over glutamatergic neuronal cell fate in the spinal cord dorsal horn. Development (Cambridge, England) 182 16291784
2007 Ptf1a is essential for the differentiation of GABAergic and glycinergic amacrine cells and horizontal cells in the mouse retina. Development (Cambridge, England) 167 17301087
2008 Pdx-1 and Ptf1a concurrently determine fate specification of pancreatic multipotent progenitor cells. Developmental biology 151 18294628
1998 p48/STAT-1alpha-containing complexes play a predominant role in induction of IFN-gamma-inducible protein, 10 kDa (IP-10) by IFN-gamma alone or in synergy with TNF-alpha. Journal of immunology (Baltimore, Md. : 1950) 149 9794404
2002 Sequential binding of UV DNA damage binding factor and degradation of the p48 subunit as early events after UV irradiation. Nucleic acids research 139 12034848
1998 p48 Activates a UV-damaged-DNA binding factor and is defective in xeroderma pigmentosum group E cells that lack binding activity. Molecular and cellular biology 139 9632823
1995 Chromosomal localization and cDNA cloning of the genes (DDB1 and DDB2) for the p127 and p48 subunits of a human damage-specific DNA binding protein. Genomics 135 8530102
2015 The acinar differentiation determinant PTF1A inhibits initiation of pancreatic ductal adenocarcinoma. eLife 130 26151762
1997 The translation initiation factor eIF3-p48 subunit is encoded by int-6, a site of frequent integration by the mouse mammary tumor virus genome. The Journal of biological chemistry 130 9295280
2007 Cerebellar GABAergic progenitors adopt an external granule cell-like phenotype in the absence of Ptf1a transcription factor expression. Proceedings of the National Academy of Sciences of the United States of America 125 17360405
1997 Stat2 is a transcriptional activator that requires sequence-specific contacts provided by stat1 and p48 for stable interaction with DNA. The Journal of biological chemistry 119 9020188
2000 Human damage-specific DNA-binding protein p48. Characterization of XPE mutations and regulation following UV irradiation. The Journal of biological chemistry 116 10777490
2001 The p48 subunit of the damaged-DNA binding protein DDB associates with the CBP/p300 family of histone acetyltransferase. Mutation research 112 11425514
1997 Distinct STAT structure promotes interaction of STAT2 with the p48 subunit of the interferon-alpha-stimulated transcription factor ISGF3. The Journal of biological chemistry 111 9242679
1996 ISGF3 gamma p48, a specificity switch for interferon activated transcription factors. Cytokine & growth factor reviews 110 8864350
1996 Molecular cloning of human p48, a transient component of progesterone receptor complexes and an Hsp70-binding protein. Molecular endocrinology (Baltimore, Md.) 108 8721986
2004 Evolutionary conserved role of ptf1a in the specification of exocrine pancreatic fates. Developmental biology 91 15031114
2003 True XP group E patients have a defective UV-damaged DNA binding protein complex and mutations in DDB2 which reveal the functional domains of its p48 product. Human molecular genetics 90 12812979
2001 p48 subunit of mouse PTF1 binds to RBP-Jkappa/CBF-1, the intracellular mediator of Notch signalling, and is expressed in the neural tube of early stage embryos. Genes to cells : devoted to molecular & cellular mechanisms 85 11318877
2006 Combined ectopic expression of Pdx1 and Ptf1a/p48 results in the stable conversion of posterior endoderm into endocrine and exocrine pancreatic tissue. Genes & development 83 16751182
2008 Ptf1a, Lbx1 and Pax2 coordinate glycinergic and peptidergic transmitter phenotypes in dorsal spinal inhibitory neurons. Developmental biology 82 18634777
2008 Transcriptional autoregulation controls pancreatic Ptf1a expression during development and adulthood. Molecular and cellular biology 80 18606784
2003 Norwalk virus nonstructural protein p48 forms a complex with the SNARE regulator VAP-A and prevents cell surface expression of vesicular stomatitis virus G protein. Journal of virology 78 14557663
2007 Origin of climbing fiber neurons and their developmental dependence on Ptf1a. The Journal of neuroscience : the official journal of the Society for Neuroscience 77 17928434
2003 The DDB2 nucleotide excision repair gene product p48 enhances global genomic repair in p53 deficient human fibroblasts. DNA repair 75 12826282
1997 Retinoic acid induces signal transducer and activator of transcription (STAT) 1, STAT2, and p48 expression in myeloid leukemia cells and enhances their responsiveness to interferons. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 73 9186002
1997 Restoration of interferon responses of adenovirus E1A-expressing HT1080 cell lines by overexpression of p48 protein. Journal of virology 73 9188575
1992 Schistosoma mansoni p48 eggshell protein gene: characterization, developmentally regulated expression and comparison to the p14 eggshell protein gene. Molecular and biochemical parasitology 73 1625706
2018 Direct reprogramming of fibroblasts into neural stem cells by single non-neural progenitor transcription factor Ptf1a. Nature communications 72 30030434
2009 Ptf1a is expressed transiently in all types of amacrine cells in the embryonic zebrafish retina. Neural development 72 19732413
2008 Graded levels of Ptf1a differentially regulate endocrine and exocrine fates in the developing pancreas. Genes & development 71 18519637
2002 Malignant transformation by the eukaryotic translation initiation factor 3 subunit p48 (eIF3e). FEBS letters 71 11904180
2001 Reduced expression of INT-6/eIF3-p48 in human tumors. International journal of oncology 71 11115556
2014 Specification of spatial identities of cerebellar neuron progenitors by ptf1a and atoh1 for proper production of GABAergic and glutamatergic neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 70 24695699
2007 Ptf1a binds to and activates area III, a highly conserved region of the Pdx1 promoter that mediates early pancreas-wide Pdx1 expression. Molecular and cellular biology 70 17403901
2016 Transcriptional Maintenance of Pancreatic Acinar Identity, Differentiation, and Homeostasis by PTF1A. Molecular and cellular biology 65 27697859
2003 p53 responsive nucleotide excision repair gene products p48 and XPC, but not p53, localize to sites of UV-irradiation-induced DNA damage, in vivo. Carcinogenesis 64 12771027
2004 Differential requirement for ptf1a in endocrine and exocrine lineages of developing zebrafish pancreas. Developmental biology 63 15183727
2003 Impaired regulation of tumor suppressor p53 caused by mutations in the xeroderma pigmentosum DDB2 gene: mutual regulatory interactions between p48(DDB2) and p53. Molecular and cellular biology 63 14560002
2004 Differential requirement for ptf1a in endocrine and exocrine lineages of developing zebrafish pancreas. Developmental biology 62 15570689
1996 Germ cell-specific DNA and RNA binding proteins p48/52 are expressed at specific stages of male germ cell development and are present in the chromatoid body. Molecular reproduction and development 60 8722687
2007 Ptf1a triggers GABAergic neuronal cell fates in the retina. BMC developmental biology 59 17910758
2015 Tfap2a and 2b act downstream of Ptf1a to promote amacrine cell differentiation during retinogenesis. Molecular brain 58 25966682
2008 Reduction of Ptf1a gene dosage causes pancreatic hypoplasia and diabetes in mice. Diabetes 58 18591390
2011 Ptf1a-mediated control of Dll1 reveals an alternative to the lateral inhibition mechanism. Development (Cambridge, England) 55 22096075
2008 Generation and characterization of Ptf1a antiserum and localization of Ptf1a in relation to Nkx6.1 and Pdx1 during the earliest stages of mouse pancreas development. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 51 18347078
1998 Primase activity of human DNA polymerase alpha-primase. Divalent cations stabilize the enzyme activity of the p48 subunit. The Journal of biological chemistry 50 9705292
2011 Suppression of Ptf1a activity induces acinar-to-endocrine conversion. Current biology : CB 48 21497092
2009 Neurog2 is a direct downstream target of the Ptf1a-Rbpj transcription complex in dorsal spinal cord. Development (Cambridge, England) 48 19641016
2006 P48 is a predictive marker for outcome of postoperative interferon-alpha treatment in patients with hepatitis B virus infection-related hepatocellular carcinoma. Cancer 48 16948122
1997 Interferon gamma-induced transcription of the murine ISGF3gamma (p48) gene is mediated by novel factors. Proceedings of the National Academy of Sciences of the United States of America 48 8990168
1992 Evolutionary conserved nucleotides within the E.coli 4.5S RNA are required for association with P48 in vitro and for optimal function in vivo. Nucleic acids research 48 1281314
2007 Differential ability of Ptf1a and Ptf1a-VP16 to convert stomach, duodenum and liver to pancreas. Developmental biology 46 17320068
2012 RNA profiling and chromatin immunoprecipitation-sequencing reveal that PTF1a stabilizes pancreas progenitor identity via the control of MNX1/HLXB9 and a network of other transcription factors. Molecular and cellular biology 45 22232429
2008 A highly conserved baculovirus gene p48 (ac103) is essential for BV production and ODV envelopment. Virology 44 18656219
2005 Genetic and antigenic characterization of the surface lipoprotein P48 of Mycoplasma bovis. Veterinary microbiology 44 15985342
2012 Endogenous n-3 polyunsaturated fatty acids delay progression of pancreatic ductal adenocarcinoma in Fat-1-p48(Cre/+)-LSL-Kras(G12D/+) mice. Neoplasia (New York, N.Y.) 43 23308056
2000 Protein-protein interactions of the primase subunits p58 and p48 with simian virus 40 T antigen are required for efficient primer synthesis in a cell-free system. The Journal of biological chemistry 43 10747950
1987 42S p48--the most abundant protein in previtellogenic Xenopus oocytes--resembles elongation factor 1 alpha structurally and functionally. The EMBO journal 42 2444435
2018 Transcription factor Ptf1a in development, diseases and reprogramming. Cellular and molecular life sciences : CMLS 41 30470852
2014 Transformation of the cerebellum into more ventral brainstem fates causes cerebellar agenesis in the absence of Ptf1a function. Proceedings of the National Academy of Sciences of the United States of America 40 24733890
2013 Genome-wide expression analysis of Ptf1a- and Ascl1-deficient mice reveals new markers for distinct dorsal horn interneuron populations contributing to nociceptive reflex plasticity. The Journal of neuroscience : the official journal of the Society for Neuroscience 40 23616538
2013 The Prdm13 histone methyltransferase encoding gene is a Ptf1a-Rbpj downstream target that suppresses glutamatergic and promotes GABAergic neuronal fate in the dorsal neural tube. Developmental biology 40 24370451
2008 Exdpf is a key regulator of exocrine pancreas development controlled by retinoic acid and ptf1a in zebrafish. PLoS biology 40 19067490
1995 The mouse DNA polymerase alpha-primase subunit p48 mediates species-specific replication of polyomavirus DNA in vitro. Molecular and cellular biology 40 7862163
2001 Impaired alpha-interferon signaling in transitional cell carcinoma: lack of p48 expression in 5637 cells. Cancer research 37 11280796
2012 Inhibition of pancreatic intraepithelial neoplasia progression to carcinoma by nitric oxide-releasing aspirin in p48(Cre/+)-LSL-Kras(G12D/+) mice. Neoplasia (New York, N.Y.) 36 23019409
2009 Multiple transcriptional mechanisms control Ptf1a levels during neural development including autoregulation by the PTF1-J complex. The Journal of neuroscience : the official journal of the Society for Neuroscience 36 19741120
2001 Moe1 and spInt6, the fission yeast homologues of mammalian translation initiation factor 3 subunits p66 (eIF3d) and p48 (eIF3e), respectively, are required for stable association of eIF3 subunits. The Journal of biological chemistry 36 11705997
2004 PTF1alpha/p48 transcription factor couples proliferation and differentiation in the exocrine pancreas [corrected]. Gastroenterology 34 15362048
2000 Role of the basic helix-loop-helix transcription factor p48 in the differentiation phenotype of exocrine pancreas cancer cells. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 34 10768861
1997 The interferon-inducible murine p48 (ISGF3gamma) gene is regulated by protooncogene c-myc. Proceedings of the National Academy of Sciences of the United States of America 34 9207073
2013 Program specificity for Ptf1a in pancreas versus neural tube development correlates with distinct collaborating cofactors and chromatin accessibility. Molecular and cellular biology 32 23754747
2012 Tlx1/3 and Ptf1a control the expression of distinct sets of transmitter and peptide receptor genes in the developing dorsal spinal cord. The Journal of neuroscience : the official journal of the Society for Neuroscience 32 22723691
2016 Loss of Ptf1a Leads to a Widespread Cell-Fate Misspecification in the Brainstem, Affecting the Development of Somatosensory and Viscerosensory Nuclei. The Journal of neuroscience : the official journal of the Society for Neuroscience 31 26937009
2011 Ptf1a/Rbpj complex inhibits ganglion cell fate and drives the specification of all horizontal cell subtypes in the chick retina. Developmental biology 30 21839069
2000 Expression and antigenic characterization of recombinant Mycoplasma agalactiae P48 major surface protein. Veterinary microbiology 30 10703704
1999 Retinoic acid resistance in NB4 APL cells is associated with lack of interferon alpha synthesis Stat1 and p48 induction. Oncogene 30 10435617
1999 p48 (ISGF-3gamma) is involved in interferon-alpha-induced suppression of hepatitis B virus enhancer-1 activity. The Journal of biological chemistry 30 10497156
2011 Long isoform of ErbB3 binding protein, p48, mediates protein kinase B/Akt-dependent HDM2 stabilization and nuclear localization. Experimental cell research 29 21930127
2004 Increased expression of hypoxia-inducible factor-1alpha, p48, and the Notch signaling cascade during acute pancreatitis in mice. Pancreas 29 14707731
2013 Insights into eukaryotic primer synthesis from structures of the p48 subunit of human DNA primase. Journal of molecular biology 28 24239947
1999 WD repeats of the p48 subunit of chicken chromatin assembly factor-1 required for in vitro interaction with chicken histone deacetylase-2. The Journal of biological chemistry 28 10347232
2009 A Turkish newborn infant with cerebellar agenesis/neonatal diabetes mellitus and PTF1A mutation. Genetic counseling (Geneva, Switzerland) 27 19650412
2014 A conserved role for p48 homologs in protecting dopaminergic neurons from oxidative stress. PLoS genetics 26 25340742