Carboxy-terminal domain phosphatase 1 (CTDP1)

Carboxy-terminal domain phosphatase 1 (CTDP1) is a pivotal enzyme that processively dephosphorylates the serine residues (Ser2 and Ser5) in the heptad repeats of the C-terminal domain of the largest RNA polymerase II subunit (POLR2A), thereby facilitating the recycling of RNA polymerase II and enabling initiation and elongation during gene transcription. CTDP1 interacts directly with transcription factors such as TFIIF and plays a non-redundant essential role in transcriptional regulation in all eukaryotic cells. It is further implicated in cell cycle progression via dephosphorylation of critical mitotic regulators and has a key role in the DNA damage response, modulating components of the Fanconi anemia and BRCA pathways. Loss-of-function mutations in CTDP1 cause the congenital cataracts, facial dysmorphism, and neuropathy (CCFDN) syndrome, and altered expression is linked to cancer cell survival and DNA repair capacity. CTDP1 is thus both fundamental for normal physiology and considered a candidate therapeutic target in specific malignancies, but its essential and broad cellular roles present considerable challenges for safe therapeutic intervention.

Other names

FCP1RNA polymerase II subunit A C-terminal domain phosphataseTFIIF-associating CTD phosphatase 1CCFDNSerine phosphatase FCP1aRNA polymerase II subunit A C-terminal domain phosphatase isoform FCP1a/bCTDP1_HUMANCTD (carboxy-terminal domain, RNA polymerase II, polypeptide A) phosphatase, subunit 1CTD of POLR2A, phosphatase of, subunit 1

Not applicable (no approved drugs that directly target CTDP1; experimental inhibition or knockdown impairs transcription, DNA repair, and cell proliferation)