Selective Dephosphorylation by SCP1 and PP2A in Phosphorylated Residues of SMAD2

摘要

Protein phosphatase is important for cellular events, and a family of protein phosphatases, the so-called C-terminal domain (CTD) of RNA polymerase II (RNAPII) phosphatases, has recently attracted attention. The CTD is the largest subunit of RNAPII and consists of a tandem repeated heptapeptide (Y1S2P3T4S5P6S7). Seven active CTD phosphatases in the human genome are known and share the same catalytic domain architecture and DXDX(T/V) active site motif. Small CTD phosphatase 1 (SCP1) dephosphor-ylates the fifth phosphorylated serine of Y1S2P3T4S5P6S7 in the CTD and has been renamed CTD small phosphatase 1 (CTDSP1). Small CTD phosphatase 2 (SCP2) and small CTD phosphatase 3 (SCP3) have a similar sequence, three-dimensional structure, and biochemical function to SCP1.3 Small CTD phosphatases (SCPs, SCP1, SCP2, and SCP3) have been identified as a conserved regulators of neuronal stem cell development through silencing of neuronal genes via co-repression of the repressor element 1 (RE-1) silencing transcription factoreuron-restrictive silencer factor (REST/ NRSF). In addition, several intracellular signaling pathways associated with SCPs have been reported in biological studies. Some studies suggest that cell division cycle associated 3 (CdcA3) and receptor-regulated SMADs (R-SMADs) could be biological substrates of SCPs, and that SCPs are involved in signaling pathways of cell cycle regulation and cell differentiation.