High impact information on FCP1

• Opposing effects of Ctk1 kinase and Fcp1 phosphatase at Ser 2 of the RNA polymerase II C-terminal domain [1].
• Furthermore, mutations in the Fcp1 CTD phosphatase lead to increased levels of Ser 2 phosphorylation [1].
• The CTD kinase, Kin28, is required for binding, and the CTD phosphatase, Fcp1, is required for dissociation of capping enzymes from the elongation complex [2].
• We report the X-ray structure of the small CTD phosphatase Scp1, which is homologous to the Fcp1 catalytic domain [3].
• Remarkably, we find that cells lacking Sub1 display decreased accumulation of Fcp1, altered RNAP II phosphorylation and decreased crosslinking of RNAP II to transcribed genes [4].

Biological context of FCP1

• One of the essential components of a phosphatase that specifically dephosphorylates the Saccharomyces cerevisiae RNA polymerase II (RPII) large subunit C-terminal domain (CTD) is a novel polypeptide encoded by an essential gene termed FCP1 [5].
• Fcp1 de-phosphorylates the RNA polymerase II (RNAPII) C-terminal domain (CTD) in vitro, and mutation of the yeast FCP1 gene results in global transcription defects and increased CTD phosphorylation levels in vivo [6].
• Our data suggest that the location or extent of CTD phosphorylation might be altered in response to DNA damage, and that the modified CTD, ESS1, and FCP1 all contribute to cellular survival in such conditions [7].
• The presence of a suppressor centromere affected the level of Fcp1 protein and the overall phosphorylation state of RNA polymerase II (RNAPII) in fcp1-2 cells, but not wild-type cells, grown at both permissive and non-permissive temperatures [8].
• We have used deletion and point mutations in Fcp1p, a TFIIF-interacting CTD phosphatase, to show that the integrity of its BRCT domain, like that of its catalytic domain, is important for cell viability, mRNA synthesis, and CTD dephosphorylation in vivo [9].

Associations of FCP1 with chemical compounds

• Furthermore, by chemical cross-linking, glutathione S-transferase pulldown, and affinity chromatography, the Fcp1-interacting subunit of pol II was identified as Rpb4, which plays regulatory roles in transcription [10].
• Surprisingly, highly purified yeast Fcp1 dephosphorylates serine 5 but not serine 2 of the RNAPII CTD repeat [6].
• Recombinant Fcp1 catalyzed the metal-dependent hydrolysis of para-nitrophenyl phosphate with a pH optimum of 5.5 (kcat = 2 s(-1); K(m) = 19 mm) [11].
• Using equivalent concentrations (25 microm) of CTD peptides of identical amino acid sequence and phosphoserine content, which differed only in the positions of phosphoserine within the heptad, we found that Fcp1 was 10-fold more active in dephosphorylating Ser2-PO4 than Ser5-PO4 [11].
• Interestingly, the Fcp1 reaction mechanism appears to entail phosphoryl transfer from RNAPII0 directly to Fcp1 [6].

Physical interactions of FCP1

• Two portions of this carboxy-terminal region of Fcp1p bound directly to the first cyclin-like repeat in the core domain of the general transcription factor TFIIB, as well as to the RAP74 subunit of TFIIF [9].
• In this report, we provide evidence that Ssu72 is a phosphatase that physically interacts with the CTD kinase Kin28 and functionally interacts with the CTD phosphatase Fcp1 [12].

Regulatory relationships of FCP1

• Here we confirm that the CTD phosphatase Fcp1 can suppress a Pin1 mutation in yeast [13].

Other interactions of FCP1

• These results suggest strongly that this KEFGK motif in RAP74 mediates its interaction with Fcp1p in vivo [9].
• This result indicates the importance of Fcp1-Rpb4 interaction for formation of the Fcp1/TFIIF/pol II complex in vivo [10].
• In addition to the pol II subunits, the complex was found to contain three subunits of a transcription factor TFIIF (TFIIF alpha, TFIIF beta, and Tfg3) and TFIIF-interacting CTD-phosphatase Fcp1 [10].

Analytical, diagnostic and therapeutic context of FCP1

• From sequence alignments, we identified a conserved acidic/hydrophobic region in FCP1 adjacent to its highly conserved BRCT domain [14].

References