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Showing CTDP1 — FCP1 is a alias.

CTDP1

RNA polymerase II subunit A C-terminal domain phosphatase · UniProt Q9Y5B0

Length
961 aa
Mass
104.4 kDa
Annotated
2026-06-09
49 papers in source corpus 34 papers cited in narrative 34 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CTDP1 (FCP1) is the essential, catalytic phosphoserine phosphatase that resets the phosphorylation state of the RNA polymerase II C-terminal domain (CTD), coupling this activity to both the transcription cycle and to cell-cycle progression (PMID:9765293, PMID:11934898, PMID:22692537). It is a member of the DXD phosphotransferase superfamily that acts through an acylphosphatase (aspartylphosphate) mechanism: structures captured at the aspartylphosphate intermediate and transition state, together with systematic active-site mutagenesis, define a Y-shaped enzyme with an acylphosphatase domain at the base of a deep canyon flanked by an FCP1-specific helical domain and a BRCT domain, and a catalytic DxDxT motif (Asp170/Asp172) required for activity (PMID:11934898, PMID:12556522, PMID:19026779). The enzyme preferentially dephosphorylates Ser2-PO4 of the CTD heptad over Ser5-PO4, opposing the Ser2 kinase to regulate elongating polymerase, and it recognizes the CTD directly and distributively rather than through a docking site on the globular polymerase (PMID:11751637, PMID:11934898, PMID:14701811, PMID:16301539). Catalytic activity and recruitment are regulated through CTDP1's intrinsically disordered C-terminus, which folds into an alpha-helix only upon binding the RAP74 (winged-helix) subunit of TFIIF, an interaction resolved by both crystal and NMR structures and further enhanced by CK2 phosphorylation of FCP1 at sites adjacent to its RAP74-binding regions (PMID:12138108, PMID:12591941, PMID:12732728, PMID:15723518). By maintaining a pool of initiation-competent unphosphorylated Pol II, CTDP1 supports transcription elongation and reinitiation (PMID:12370301, PMID:22733996). Independently of transcription, CTDP1 drives mitotic exit: it dephosphorylates Greatwall kinase to reactivate PP2A-B55 and also acts on Wee1, Cdc20, and Ensa/ARPP19, coordinating Cdk1 inactivation as a dephosphorylation switch (PMID:22692537, PMID:26653855, PMID:24391510). Through its BRCT domain it additionally interacts with FANCI to promote DNA damage-induced foci formation and homologous recombination repair (PMID:31240132). Loss of Ctdp1 in mouse embryos is lethal and causes cell-cycle arrest in fibroblasts, underscoring its essentiality (PMID:33408128).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1998 High

    Establishing the core identity of CTDP1 answered what enzyme removes phosphates from the Pol II CTD, identifying FCP1 as an essential RAP74-stimulated phosphatase within the Pol II holoenzyme.

    Evidence Two-hybrid screen, phosphatase assays, and co-purification of FCP1 with the Pol II holoenzyme and TFIIF RAP74

    PMID:9765293

    Open questions at the time
    • Catalytic mechanism and active-site residues undefined
    • Ser2 vs Ser5 specificity not yet resolved
  2. 2001 High

    ChIP and genetic epistasis placed FCP1 in opposition to a CTD Ser2 kinase on elongating polymerase, defining its physiological role in the transcription cycle.

    Evidence In vivo ChIP across promoter and coding regions plus Fcp1 mutant analysis with phospho-specific antibodies in yeast

    PMID:11751637

    Open questions at the time
    • Did not establish biochemical substrate preference in vitro
    • Recruitment mechanism to elongating polymerase unclear
  3. 2001 Medium

    Xenopus extract immunodepletion showed FCP1 accounts for all CTD phosphatase activity and can act on free, non-transcribing polymerase, the first hint of a transcription-independent role.

    Evidence Immunodepletion of xFCP1 from egg extracts and CTD phosphatase assays upon calcium activation

    PMID:11533226

    Open questions at the time
    • Specific non-transcriptional substrates not identified
    • Single extract system, not validated in intact cells
  4. 2002 High

    In vitro reconstitution with defined CTD substrates established Ser2 preference, the DxDxT catalytic motif, and the requirement of the BRCT domain, defining the catalytic core.

    Evidence Recombinant fission-yeast Fcp1, synthetic CTD phosphopeptide assays, deletion and site-directed mutagenesis

    PMID:11934898

    Open questions at the time
    • Atomic-resolution active-site geometry not yet determined
    • Ser2/Ser5 preference later contradicted in budding yeast
  5. 2002 High

    Characterizing the FCP1-TFIIF-Pol II complex identified the polymerase contact (Rpb4) and showed elongation stimulation can be separated from TFIIF, broadening FCP1's functional repertoire.

    Evidence FLAG affinity purification, cross-linking, GST pulldown, and in vitro transcription elongation/genetic epistasis assays in fission yeast

    PMID:11839823 PMID:12370301

    Open questions at the time
    • Molecular basis of elongation stimulation unresolved
    • How phosphatase vs elongation activities are partitioned unclear
  6. 2003 High

    Crystal and NMR structures of the RAP74-FCP1 interface revealed coupled folding-upon-binding of the disordered FCP1 C-terminus, explaining how TFIIF recruits and stimulates the phosphatase.

    Evidence X-ray co-crystal and NMR solution structures of cterRAP74 bound to cterFCP1

    PMID:12591941 PMID:12732728

    Open questions at the time
    • Did not resolve the catalytic-domain structure
    • Coupling of binding to catalytic stimulation not structurally explained
  7. 2003 High

    Systematic mutagenesis and substrate dissection mapped the full active site, defined distributive single-heptad catalysis, and placed FCP1 in the DXD phosphotransferase superfamily.

    Evidence Alanine scanning across 14 positions, synthetic CTD peptides, mass spectrometry in fission yeast

    PMID:12556522 PMID:14701811

    Open questions at the time
    • Reaction intermediates not yet visualized structurally
    • How distributive kinetics relate to in vivo CTD processing unclear
  8. 2003 Medium

    Defining CK2 as an upstream regulatory kinase showed FCP1 activity and RAP74 binding are tuned by phosphorylation of FCP1 itself, establishing a regulatory input.

    Evidence In vitro kinase assays, NMR, FT-ICR MS, and binding assays mapping CK2 sites (T584, S942/S944) in Xenopus and human FCP1

    PMID:12138108 PMID:12591939 PMID:15723518

    Open questions at the time
    • In vivo significance of individual sites not dissected
    • Whether CK2 regulation operates in mitotic substrate dephosphorylation unknown
  9. 2004 Medium

    Mechanistic dissection of catalysis and modulation showed direct phosphoryl transfer, random-access CTD recognition, and inhibition by competing phospho-CTD binders, but exposed a Ser2/Ser5 specificity discrepancy across organisms.

    Evidence In vitro phosphoryl-transfer, Pol II interaction, and inhibition assays with Pin1/Hce1/CA150

    PMID:11904169 PMID:14672652 PMID:15563457 PMID:15670829 PMID:16301539

    Open questions at the time
    • Ser2 vs Ser5 specificity unresolved between budding and fission yeast
    • Physiological relevance of PRMT5 methylation of FCP1 not established
  10. 2008 High

    Transition-state structures resolved the acylphosphatase mechanism and CTD-threading geometry, providing the definitive catalytic model and distinguishing FCP1 from the related Scp1 enzyme.

    Evidence X-ray crystallography with Mg-BeF3 and Mg-AlF4 transition-state analogues plus mutagenesis; 1.45 A structure with Spt5 CTD substrate assays

    PMID:19026779 PMID:25883047

    Open questions at the time
    • Structure of the full enzyme engaging intact Pol II not determined
    • Regulation of substrate choice (Pol II CTD vs Spt5) in cells unclear
  11. 2012 High

    Identifying mitotic substrates established a transcription-independent role for FCP1 in MPF inactivation, redefining it as a cell-cycle phosphatase.

    Evidence Biochemical fractionation, genetic epistasis, and in vitro dephosphorylation of Cdc20, USP44, and Wee1; ChIP and catalytic-dead rescue for the Pol II pool

    PMID:22692537 PMID:22733996

    Open questions at the time
    • Spatiotemporal coordination of transcriptional vs mitotic functions unclear
    • How substrate selectivity is achieved in mitosis not defined
  12. 2015 High

    Placing FCP1 upstream of the Greatwall-Ensa-PP2A-B55 axis showed it dephosphorylates Greatwall and Ensa/ARPP19 to drive a dephosphorylation switch at mitotic exit and to govern mitotic slippage via Wee1.

    Evidence Co-IP, in vitro dephosphorylation, kinase activity assays, and mathematical modelling in human cells and extracts

    PMID:24391510 PMID:25744022 PMID:26653855

    Open questions at the time
    • Hierarchy among multiple mitotic phosphatases not fully quantified
    • Regulation of FCP1 targeting to mitotic substrates unknown
  13. 2019 Medium

    BRCT-mediated interaction with FANCI extended CTDP1's function into DNA interstrand crosslink repair and homologous recombination.

    Evidence Co-IP, chromatin fractionation, foci formation, and HR efficiency assays with knockdown

    PMID:31240132

    Open questions at the time
    • Whether phosphatase activity is required for the repair role unclear
    • Direct substrate within the FA/HR pathway not identified
  14. 2025 Medium

    Identifying RPB7 as a recruitment factor showed CTDP1 maintains RPB1 stability and supports Pol II reinitiation, linking CTD dephosphorylation to polymerase turnover.

    Evidence RPB7 depletion, Co-IP of RPB7-CTDP1, RPB1 stability western blots, and Cullin 3 ubiquitin ligase identification

    PMID:40038320

    Open questions at the time
    • Direct demonstration that CTDP1 catalysis protects RPB1 from degradation incomplete
    • Single-lab Co-IP without reciprocal structural validation

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CTDP1 partitions and is targeted between its transcriptional, mitotic, and DNA-repair functions, and which regulatory inputs control this in vivo, remains unresolved.
  • No unified model of substrate selection across contexts
  • Role of the BRCT domain in distinguishing transcription vs repair partners unclear
  • In vivo regulation of mitotic substrate engagement undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 4 GO:0140096 catalytic activity, acting on a protein 4 GO:0140110 transcription regulator activity 3
Localization
GO:0000228 nuclear chromosome 2 GO:0005634 nucleus 1
Pathway
R-HSA-1640170 Cell Cycle 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-73894 DNA Repair 1
Partners
CDC20FANCIGREATWALLRAP74RPB2RPB4RPB7WEE1
Complex memberships
RNA polymerase II holoenzymeTFIIF

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 FCP1 (CTDP1) was identified as an essential subunit of a RAP74-stimulated phosphatase that processively dephosphorylates the CTD of the largest RNA polymerase II subunit, and as a stoichiometric component of a human RNA polymerase II holoenzyme complex. FCP1 interacts with the evolutionarily conserved carboxyl-terminal domain of the RAP74 subunit of TFIIF. Two-hybrid screen, biochemical phosphatase assay, co-purification The Journal of biological chemistry High 9765293
2001 In yeast, Fcp1 CTD phosphatase opposes Ctk1 kinase at Ser2 of the RNA polymerase II CTD: mutations in Fcp1 lead to increased Ser2 phosphorylation, and Fcp1 cross-links to both promoter and coding regions, indicating association with elongating polymerase. In vivo chromatin immunoprecipitation (ChIP), genetic mutant analysis, phospho-specific antibodies Genes & development High 11751637
2002 Fcp1 from fission yeast displays an inherent 10-fold preference for dephosphorylating Ser2-PO4 over Ser5-PO4 of the CTD heptad, and catalytic activity requires a DxDxT motif (Asp170/Asp172); a BRCT domain (aa 487–580) is also essential for activity. Recombinant protein expression in bacteria, in vitro phosphatase assays with synthetic CTD phosphopeptides, deletion and site-directed mutagenesis The Journal of biological chemistry High 11934898
2002 In fission yeast, Fcp1 forms a complex with TFIIF (TFIIFα, TFIIFβ, Tfg3) and RNA polymerase II containing non-phosphorylated CTD. The Fcp1-interacting subunit of Pol II was identified as Rpb4 via chemical cross-linking, GST pulldown, and affinity chromatography; Rpb4 repression reduces Fcp1 association with the complex and increases phosphorylated Rpb1 levels. Immunoaffinity purification (FLAG-tagged Rpb3 and Fcp1), in vitro CTD phosphatase assay, chemical cross-linking, GST pulldown, affinity chromatography, thiamine-dependent repression Molecular and cellular biology High 11839823
2002 FCP1 stimulates transcription elongation by RNA polymerase II in vitro and in vivo, independently of TFIIF; the elongation activities of TFIIF and FCP1 are additive. Genetic fcp1 alleles are lethal when combined with mutations in the second-largest subunit of RNAP II affecting elongation. In vitro transcription elongation assays, genetic suppressor analysis, genetic epistasis (double mutants) Molecular and cellular biology High 12370301
2002 Pin1 PPIase activity stimulates Fcp1-mediated CTD dephosphorylation in vitro, specifically enhancing dephosphorylation at Ser5-Pro (but not Ser2-Pro) in yeast, indicating that cis/trans prolyl isomerization of the CTD modulates its accessibility to Fcp1. Genetic interaction: Fcp1 suppresses a Pin1 mutation in yeast, requiring both the phosphatase and BRCT domains of Fcp1. Yeast genetic suppressor assay, in vitro CTD dephosphorylation assay with recombinant proteins, phospho-specific antibodies FEBS letters Medium 11904169
2002 CK2 phosphorylates xFCP1 mainly at a cluster of serines centered on Ser457 in Xenopus laevis; CK2-dependent phosphorylation enhances FCP1 CTD phosphatase activity 4-fold and its binding to the RAP74 subunit of TFIIF. Biochemical fractionation, kinase assays, drug sensitivity, in vitro phosphatase assays The Journal of biological chemistry Medium 12138108
2003 Crystal structure of the winged-helix domain of human RAP74 bound to the C-terminal alpha-helical segment of FCP1 (residues 944–961) reveals the molecular basis for TFIIF-FCP1 interaction: hydrophobic and electrostatic contacts between the H2/H3 helices of RAP74 and the H1' helix of FCP1. X-ray crystallography (co-crystal structure) Proceedings of the National Academy of Sciences of the United States of America High 12591941
2003 NMR solution structure of the cterRAP74–cterFCP1 complex shows that the C-terminus of FCP1 (residues 879–961) is intrinsically disordered in the unbound state but forms an alpha-helix (H1'; E945–M961) upon binding RAP74; the binding interface relies on hydrophobic van der Waals contacts and electrostatic interactions between acidic residues of FCP1 and lysines of RAP74. NMR spectroscopy (high-resolution solution structure) Proceedings of the National Academy of Sciences of the United States of America High 12732728
2003 Fcp1 active site consists of at least seven conserved residues (Asp170, Asp172, Arg223, Asp258, Lys280, Asp297, Asp298 in S. pombe); alanine substitutions at each abolish phosphatase activity. The minimal phosphatase domain spans aa 156–580. Five residues are conserved with T4 polynucleotide 3'-phosphatase, indicating Fcp1 belongs to the DXD phosphotransferase superfamily. Site-directed mutagenesis, deletion analysis, in vitro phosphatase assays The Journal of biological chemistry High 12556522
2003 Fcp1 acts distributively (not processively) on tandem Ser2-PO4 CTD heptads; the minimal optimal CTD substrate is a single heptad; flanking residues Tyr1 and Pro3 of the heptad are important for phosphatase activity. Thr174, Tyr237, Thr243, Tyr249 are identified as additional active site residues. In vitro phosphatase assays with synthetic CTD phosphopeptides, alanine scanning mutagenesis, mass spectrometry The Journal of biological chemistry High 14701811
2003 FCP1 phosphorylation by CK2 at sites adjacent to two RAP74-binding regions (central domain T584; C-terminal domain S942–S944) enhances FCP1 binding to RAP74. CK2 phosphorylation at S942/S944 occurs in a semiordered fashion; both phosphorylations contribute to enhanced RAP74 binding. In vitro kinase assays, NMR spectroscopy, FT-ICR mass spectrometry, binding assays with purified proteins Biochemistry High 15723518
2003 Human FCP1 is a phosphoprotein phosphorylated at multiple sites in vivo; phosphorylated FCP1 (but not dephosphorylated FCP1) can physically interact with TFIIF, and only phosphorylated FCP1 has its CTD phosphatase activity stimulated by TFIIF and is more active in stimulating transcription elongation. Biochemical phosphatase assays, in vitro transcription elongation assays, co-immunoprecipitation, HeLa cell fractionation Proceedings of the National Academy of Sciences of the United States of America Medium 12591939
2003 NMR solution structure of cterRAP74 shows that cterFCP1 binds to a groove between alpha-helices H2 and H3 of RAP74 without altering RAP74 secondary structure; cterFCP1 binds an overlapping groove of TFIIB between alpha-helices D1 and E1 in its first cyclin repeat, similar to the VP16 binding site. NMR solution structure determination, NMR chemical shift mapping Biochemistry Medium 12578358
2004 Fcp1 associates with elongating RNAPII holoenzyme in vitro; CTD dephosphorylation by Fcp1 occurs preferentially when the native ternary RNAPII-DNA-RNA complex is disrupted. Highly purified yeast Fcp1 dephosphorylates Ser5 but not Ser2 of the CTD repeat (contradicts S. pombe Fcp1 data). The Fcp1 reaction mechanism involves direct phosphoryl transfer from RNAPII to Fcp1. In vitro Fcp1-RNAPII association assay, CTD dephosphorylation assays with native vs. ternary complexes, phosphoryl transfer assay The Journal of biological chemistry Medium 15563457
2004 Dephosphorylation of RNAPII CTD by FCP1 is inhibited by Pin1 and Hce1 (capping enzyme) but not by CA150; inhibition is observed with both free RNAPII and elongation complexes, indicating that phospho-CTD binding proteins can modulate FCP1 activity by steric hindrance. In vitro CTD dephosphorylation assays with purified proteins Journal of molecular biology Medium 14672652
2005 FCP1 interacts with PRMT5 methyltransferase, NDR1 kinase, RPB2 (RNAPII subunit), and ERH; FCP1 is a substrate of PRMT5-mediated methylation both in vivo and in vitro; FCP1-associated PRMT5 can methylate histone H4 in vitro. Epitope-tagged FCP1 affinity purification, mass spectrometry, co-immunoprecipitation of endogenous proteins, in vitro pull-down, in vitro methylation assay FEBS letters Medium 15670829
2005 FCP1 directly recognizes and dephosphorylates the CTD independent of the globular non-CTD part of Pol II (random access, not docking-site mechanism). FCP1 also interacts with a non-CTD region of Pol II that is functionally distinct from CTD phosphatase activity and may mediate transcription elongation stimulation. Biochemical CTD phosphatase assays, Pol II interaction assays, multiple experimental formats Proceedings of the National Academy of Sciences of the United States of America Medium 16301539
2005 HIV-1 Tat interacts with both the acidic/hydrophobic region and the BRCT domain of FCP1 (aa 562–685 required); Tat inhibits RAP74 binding to FCP1 and inhibits CK2 phosphorylation of FCP1 at the adjacent site. FCP1 is required for Tat-mediated transactivation in vitro. In vitro binding assays with purified proteins, yeast two-hybrid, in vitro transcription, CK2 phosphorylation inhibition assay Biochemistry Medium 15723517
2008 Crystal structure of Fcp1 captured at two reaction stages (Mg-BeF3 mimicking the aspartylphosphate intermediate; Mg-AlF4- mimicking the transition state) reveals Fcp1 is a Y-shaped protein with an acylphosphatase domain at the base of a deep canyon flanked by an Fcp1-specific helical domain and a BRCT domain. Mutational analysis shows Fcp1 and Scp1 use different CTD-binding modes, with the CTD threading through the Fcp1 canyon to access the active site. X-ray crystallography with transition-state analogues, site-directed mutagenesis Molecular cell High 19026779
2009 A crystal structure of S. pombe Fcp1 at 1.45 Å with Mg2+ and AlF3 (mimicking an associative phosphorane transition state) was determined. Fcp1 can dephosphorylate Thr1-PO4 of the Spt5 CTD nonamer repeat, and Arg271 governs the substrate preference between Pol2 CTD and Spt5 CTD. X-ray crystallography, in vitro phosphatase assays with synthetic Spt5 CTD peptides, site-directed mutagenesis (R271A, R299A) RNA (New York, N.Y.) High 25883047
2001 In Xenopus laevis, xFCP1 is solely responsible for CTD phosphatase activity in egg extracts; the CTD undergoes fast dephosphorylation upon fertilization attributable to xFCP1. Free (non-transcribing) RNAPII serves as an xFCP1 substrate in vivo, indicating FCP1 can act independently of transcription. cDNA cloning, immunodepletion of xFCP1 from egg extracts, CTD phosphatase assays, calcium activation of CSF-arrested extracts Molecular and cellular biology Medium 11533226
2001 Targeted recruitment of FCP1 to promoter templates via fusion to a DNA-binding domain stimulates transcription. The C-terminal region of FCP1 alone is sufficient for transcriptional activation, RAP74 binding, and nuclear localization; the N-terminal phosphatase domain and BRCT domain are not required for these activities. Transient transfection, promoter-tethering assay, in vivo binding assay Nucleic acids research Medium 11522823
2001 FCP1 directly binds HIV-1 Tat in vitro and specifically represses Tat-mediated transactivation of the HIV-1 LTR without affecting basal transcription. In vitro binding assays, transient transfection reporter assays AIDS (London, England) Low 11273209
2003 FCP1 interacts with MEP50, a component of the methylosome complex, and associates with spliceosomal U snRNP components, suggesting a role for FCP1 in linking transcription elongation with pre-mRNA splicing. Epitope-tagged FCP1 affinity purification, mass spectrometry identification, co-immunoprecipitation Nucleic acids research Low 12560496
2009 NMR structure of cterRAP74 bound to a phosphorylated peptide from the central domain of FCP1 (centFCP1-PO4, phosphorylated at T584) shows centFCP1 uses the same RAP74 groove as cterFCP1 but with significant differences in binding details, revealing the adaptability of RAP74 in recognizing two FCP1 regions. NMR spectroscopy, isothermal titration calorimetry (ITC) Biochemistry Medium 19215094
2012 Fcp1 is required for MPF (cyclin B-Cdk1) inactivation at mitosis exit in a transcription-independent manner. Fcp1 dephosphorylates Cdc20 (APC/C coactivator), USP44 (deubiquitinase), and Wee1 (Cdk1-inhibitory kinase) to promote mitotic exit. Biochemical fractionation, genetic epistasis, in vitro dephosphorylation assays, cell biology (mitotic exit assays) Nature communications High 22692537
2012 Fcp1 dephosphorylation of the RNAPII CTD is required to maintain a pool of initiation-competent unphosphorylated Pol II; Fcp1 depletion reduces Pol II occupancy in coding regions of highly transcribed heat shock genes (Hsp70, Hsp26, Hsp83) and dramatically increases phosphorylation of non-chromatin-bound Pol II. Both effects depend on Fcp1 catalytic activity. RNAi depletion in Drosophila S2 cells, ChIP, RNA measurement, reexpression of wild-type vs catalytically dead Fcp1 Molecular and cellular biology High 22733996
2014 Fcp1 mediates dephosphorylation of Ensa/ARPP19 during mitotic exit; PP2A/B55 is required for Greatwall dephosphorylation at the Cdk site Thr194. Neither Fcp1 nor PP2A depletion alone blocks bulk mitotic Cdk1 substrate dephosphorylation, indicating a hierarchy of phosphatases during mitotic exit. Mathematical modelling, phospho-specific antibody time-course experiments, depletion/inhibition in cell extracts PLoS genetics Medium 24391510
2015 Fcp1 binds Greatwall (Gwl) kinase during mitosis exit and dephosphorylates it at Cdk1 phosphorylation sites, drastically reducing Gwl kinase activity towards Ensa/ARPP19 and thereby enabling PP2A-B55 activation. Fcp1 thus coordinates Cdk1 and Gwl inactivation to generate a dephosphorylation switch driving mitosis progression. Co-immunoprecipitation, in vitro dephosphorylation assays, kinase activity assays, cell biology experiments in human cells eLife High 26653855
2015 During antimicrotubule drug-induced prolonged mitosis, Fcp1 reactivates Wee1 (via dephosphorylation), which lowers Cdk1 activity, weakens the spindle assembly checkpoint (SAC), and promotes mitotic slippage and cell survival. Wee1 inhibition counteracts this by strengthening SAC. Genetic knockdown, chemical inhibition, cell biology assays (mitotic arrest/exit, apoptosis), cancer cell lines and primary leukemia cells Cell death and differentiation Medium 25744022
2019 CTDP1 (FCP1) interacts with FANCI via its BRCT domain and regulates multiple aspects of FANCI activity including chromatin localization, interaction with γ-H2AX, and SQ motif phosphorylations. CTDP1 promotes DNA damage-induced FANCA and FANCD2 foci formation and enhances homologous recombination repair efficiency. BRCT domain-specific protein interaction network, co-immunoprecipitation, chromatin fractionation, foci formation assays, HR repair efficiency assays, knockdown Cell death discovery Medium 31240132
2021 Biallelic deletion of Ctdp1 in mouse embryos causes lethality before embryonic day 7.5. In MEFs, Ctdp1 deletion leads to G1- and G2-phase arrest, reduced S-phase population, increased p27, decreased phospho-RB, decreased phospho-Histone H3, and decreased Cyclin B, indicating a role in cell cycle progression. Conditional knockout mouse model (loxP/Cre), MEF culture, cell cycle analysis by FACS, western blotting Biology open Medium 33408128
2025 RPB7 interacts with CTDP1 and recruits it to RNA polymerase II to dephosphorylate RPB1 (the largest Pol II subunit), maintaining RPB1 stability. Depletion of RPB7 destabilizes RPB1 through a process involving CDK9, the CTD and linker of RPB1, and the E3 ubiquitin ligase Cullin 3; RPB7 is also required for Pol II reinitiation. RPB7 depletion experiments, co-immunoprecipitation (RPB7-CTDP1 interaction), western blotting for RPB1 stability, ubiquitin ligase identification Nature communications Medium 40038320

Source papers

Stage 0 corpus · 49 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Opposing effects of Ctk1 kinase and Fcp1 phosphatase at Ser 2 of the RNA polymerase II C-terminal domain. Genes & development 352 11751637
1998 FCP1, the RAP74-interacting subunit of a human protein phosphatase that dephosphorylates the carboxyl-terminal domain of RNA polymerase IIO. The Journal of biological chemistry 128 9765293
2013 WUSCHEL-RELATED HOMEOBOX4 is involved in meristem maintenance and is negatively regulated by the CLE gene FCP1 in rice. The Plant cell 120 23371950
2002 Characterization of the CTD phosphatase Fcp1 from fission yeast. Preferential dephosphorylation of serine 2 versus serine 5. The Journal of biological chemistry 84 11934898
2002 Formation of a carboxy-terminal domain phosphatase (Fcp1)/TFIIF/RNA polymerase II (pol II) complex in Schizosaccharomyces pombe involves direct interaction between Fcp1 and the Rpb4 subunit of pol II. Molecular and cellular biology 83 11839823
2008 The structure of Fcp1, an essential RNA polymerase II CTD phosphatase. Molecular cell 67 19026779
2005 Identification of proteins interacting with the RNAPII FCP1 phosphatase: FCP1 forms a complex with arginine methyltransferase PRMT5 and it is a substrate for PRMT5-mediated methylation. FEBS letters 60 15670829
2002 Pin1 modulates the dephosphorylation of the RNA polymerase II C-terminal domain by yeast Fcp1. FEBS letters 57 11904169
2012 Fcp1-dependent dephosphorylation is required for M-phase-promoting factor inactivation at mitosis exit. Nature communications 55 22692537
2002 FCP1, a phosphatase specific for the heptapeptide repeat of the largest subunit of RNA polymerase II, stimulates transcription elongation. Molecular and cellular biology 53 12370301
2014 PP2A/B55 and Fcp1 regulate Greatwall and Ensa dephosphorylation during mitotic exit. PLoS genetics 52 24391510
2009 Analysis of all protein phosphatase genes in Aspergillus nidulans identifies a new mitotic regulator, fcp1. Eukaryotic cell 51 19181872
2015 The Fcp1-Wee1-Cdk1 axis affects spindle assembly checkpoint robustness and sensitivity to antimicrotubule cancer drugs. Cell death and differentiation 37 25744022
2003 Molecular mechanism of recruitment of TFIIF- associating RNA polymerase C-terminal domain phosphatase (FCP1) by transcription factor IIF. Proceedings of the National Academy of Sciences of the United States of America 37 12591941
2003 NMR structure of a complex containing the TFIIF subunit RAP74 and the RNA polymerase II carboxyl-terminal domain phosphatase FCP1. Proceedings of the National Academy of Sciences of the United States of America 36 12732728
2004 Interaction of Fcp1 phosphatase with elongating RNA polymerase II holoenzyme, enzymatic mechanism of action, and genetic interaction with elongator. The Journal of biological chemistry 32 15563457
2015 Fcp1 phosphatase controls Greatwall kinase to promote PP2A-B55 activation and mitotic progression. eLife 30 26653855
2012 Fcp1 dephosphorylation of the RNA polymerase II C-terminal domain is required for efficient transcription of heat shock genes. Molecular and cellular biology 30 22733996
2003 Schizosaccharomyces pombe carboxyl-terminal domain (CTD) phosphatase Fcp1: distributive mechanism, minimal CTD substrate, and active site mapping. The Journal of biological chemistry 29 14701811
2002 FCP1 phosphorylation by casein kinase 2 enhances binding to TFIIF and RNA polymerase II carboxyl-terminal domain phosphatase activity. The Journal of biological chemistry 29 12138108
2012 Carbon-Detected (15)N NMR Spin Relaxation of an Intrinsically Disordered Protein: FCP1 Dynamics Unbound and in Complex with RAP74. The journal of physical chemistry letters 28 26286791
2003 The C-terminal domain phosphatase and transcription elongation activities of FCP1 are regulated by phosphorylation. Proceedings of the National Academy of Sciences of the United States of America 28 12591939
2001 Transcription-independent RNA polymerase II dephosphorylation by the FCP1 carboxy-terminal domain phosphatase in Xenopus laevis early embryos. Molecular and cellular biology 26 11533226
2004 Dephosphorylation of RNA polymerase II by CTD-phosphatase FCP1 is inhibited by phospho-CTD associating proteins. Journal of molecular biology 25 14672652
2003 Defining the active site of Schizosaccharomyces pombe C-terminal domain phosphatase Fcp1. The Journal of biological chemistry 24 12556522
2019 CTDP1 regulates breast cancer survival and DNA repair through BRCT-specific interactions with FANCI. Cell death discovery 22 31240132
2005 Fcp1 directly recognizes the C-terminal domain (CTD) and interacts with a site on RNA polymerase II distinct from the CTD. Proceedings of the National Academy of Sciences of the United States of America 22 16301539
2003 The FCP1 phosphatase interacts with RNA polymerase II and with MEP50 a component of the methylosome complex involved in the assembly of snRNP. Nucleic acids research 22 12560496
2011 The disordered C-terminus of the RNA polymerase II phosphatase FCP1 is partially helical in the unbound state. Biochemical and biophysical research communications 21 21672523
2005 Enhanced binding of RNAP II CTD phosphatase FCP1 to RAP74 following CK2 phosphorylation. Biochemistry 20 15723518
2001 Transcription activation by targeted recruitment of the RNA polymerase II CTD phosphatase FCP1. Nucleic acids research 18 11522823
2011 Atomistic simulations reveal structural disorder in the RAP74-FCP1 complex. The journal of physical chemistry. B 17 21988473
2005 Interactions of the HIV-1 Tat and RAP74 proteins with the RNA polymerase II CTD phosphatase FCP1. Biochemistry 16 15723517
2003 Solution structure of the carboxyl-terminal domain of RAP74 and NMR characterization of the FCP1-binding sites of RAP74 and human TFIIB. Biochemistry 16 12578358
2004 An encephalitozoon cuniculi ortholog of the RNA polymerase II carboxyl-terminal domain (CTD) serine phosphatase Fcp1. Biochemistry 15 15170348
2016 Quantification of Compactness and Local Order in the Ensemble of the Intrinsically Disordered Protein FCP1. The journal of physical chemistry. B 14 27551949
2009 The RNA Pol II CTD phosphatase Fcp1 is essential for normal development in Drosophila melanogaster. Gene 14 19632310
2009 NMR structure of a complex formed by the carboxyl-terminal domain of human RAP74 and a phosphorylated peptide from the central domain of the FCP1 phosphatase. Biochemistry 13 19215094
2013 Native-based simulations of the binding interaction between RAP74 and the disordered FCP1 peptide. The journal of physical chemistry. B 11 23387368
2009 NMR assignment of the intrinsically disordered C-terminal region of Homo sapiens FCP1 in the unbound state. Biomolecular NMR assignments 10 19888685
2001 Inhibition of Tat transactivation by the RNA polymerase II CTD-phosphatase FCP1. AIDS (London, England) 10 11273209
2015 Genetic and structural analysis of the essential fission yeast RNA polymerase II CTD phosphatase Fcp1. RNA (New York, N.Y.) 9 25883047
2019 Regulation of Skn7-dependent, oxidative stress-induced genes by the RNA polymerase II-CTD phosphatase, Fcp1, and Mediator kinase subunit, Cdk8, in yeast. The Journal of biological chemistry 8 31506296
2021 Ctdp1 deficiency leads to early embryonic lethality in mice and defects in cell cycle progression in MEFs. Biology open 6 33408128
2015 Lentivirus-mediated knockdown of CTDP1 inhibits lung cancer cell growth in vitro. Journal of cancer research and clinical oncology 3 26590573
2025 CTDP1 and RPB7 stabilize Pol II and permit reinitiation. Nature communications 2 40038320
2021 Transient Electrostatic Interactions between Fcp1 and Rap74 Bias the Conformational Ensemble of the Complex with Minimal Impact on Binding Affinity. The journal of physical chemistry. B 2 34550709
2012 High Fcp1 phosphatase activity contributes to setting an intense transcription rate required in Drosophila nurse and follicular cells for egg production. Gene 1 22903034
2025 The CTDP1 Founder Variant in CCFDN: Insights into Pathogenesis, Phenotypic Spectrum and Therapeutic Approaches. International journal of molecular sciences 0 41515914

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