C-terminal domain small phosphatase 1 (CTDSP1)

C-terminal domain small phosphatase 1 (CTDSP1), also known as SCP1, is a critical enzyme belonging to the haloacid dehalogenase-like hydrolase family that regulates the eukaryotic transcription cycle. Its primary function involves the specific dephosphorylation of the Ser-5 residue within the C-terminal domain (CTD) of RNA polymerase II, which is a vital step for the transition from transcription initiation to elongation (Yeo et al., 2003, UniProt Q9GZU7). CTDSP1 also functions as a transcriptional corepressor by interacting with the REST/NRSF complex to silence neuronal genes in non-neuronal cells, thereby playing a significant role in cellular differentiation (Visvanathan et al., 2007). In clinical oncology, CTDSP1 is often found dysregulated and has been implicated in the progression of various cancers by modulating the cell cycle and signaling pathways like BMP and TGF-beta (Kashuba et al., 2004). Research into small molecule inhibitors has identified compounds such as the proton pump inhibitor rabeprazole that can inhibit CTDSP1 activity, suggesting potential for drug repurposing or the development of novel therapeutics (Zhang et al., 2011). However, because CTDSP1 influences fundamental transcriptional processes, therapeutic strategies must carefully address the risks of broad-spectrum gene dysregulation and off-target effects on related phosphatases.

Other names

SCP1NIF3NLIIFCTD small phosphatase 1Nuclear LIM interactor-interacting factor 3

Inhibition of CTDSP1 phosphatase activity to modulate RNA polymerase II phosphorylation and gene expression.