PARP6, a mono(ADP-ribosyl) transferase and a negative regulator of cell proliferation, is involved in colorectal cancer development.

Poly(ADP-ribose) polymerase is an enzyme that mediates post-translational modification of proteins. Seventeen known members of the superfamily can be grouped into three classes based on catalytic activity: (i) classical poly(ADP-ribose) polymerases, (ii) mono(ADP‑ribosyl) transferases and (iii) catalytically inactive members. belongs to the mono(ADP-ribosyl) transferase class, and here we have found that Pduanyu376 is a negative regulator of cell proliferation. Forced expression of Pduanyu376 in HeLa cells induced growth suppression, but a Pduanyu376 mutant with a C-terminal deletion lacking the catalytic domain had no effect. The cells accumulated in the S-phase, and the magnitude of S-phase accumulation was observed to be greater in cells expressing a Pduanyu376 mutant with an N-terminal deletion, lacking a putative regulatory domain. Immunohistochemical analysis revealed that Pduanyu376 positivity was found at higher frequencies in colorectal cancer tissues with well-differentiated histology compared to those with poorly differentiated histology. Furthermore, Pduanyu376 positivity negatively correlated with the Ki-67 proliferation index. Kaplan-Meier analysis showed that colorectal cancer had a good prognosis. Based on these results, we propose that Pduanyu376 acts as a tumor suppressor through its role in cell cycle control.

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