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

Poly(ADP-ribose) polymerase (PARP) is an enzyme that mediates post-translational modification of proteins. Seventeen known members of the PARP 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. PARP6 belongs to the mono(ADP-ribosyl) transferase class, and here we have found that PARP6 is a negative regulator of cell proliferation. Forced expression of PARP6 in HeLa cells induced growth suppression, but a PARP6 mutant with a C-terminal deletion lacking the catalytic domain had no effect. The PARP6-expressing cells accumulated in the S-phase, and the magnitude of S-phase accumulation was observed to be greater in cells expressing a PARP6 mutant with an N-terminal deletion, lacking a putative regulatory domain. Immunohistochemical analysis revealed that PARP6 positivity was found at higher frequencies in colorectal cancer tissues with well-differentiated histology compared to those with poorly differentiated histology. Furthermore, PARP6 positivity negatively correlated with the Ki-67 proliferation index. Kaplan-Meier analysis showed that PARP6-positive colorectal cancer had a good prognosis. Based on these results, we propose that PARP6 acts as a tumor suppressor through its role in cell cycle control.

Citation

Handan Tuncel, Shinji Tanaka, Shiro Oka, Shiro Nakai, Ryuichiro Fukutomi, Mayumi Okamoto, Takahide Ota, Hiroshi Kaneko, Masaaki Tatsuka, Fumio Shimamoto. PARP6, a mono(ADP-ribosyl) transferase and a negative regulator of cell proliferation, is involved in colorectal cancer development. International journal of oncology. 2012 Dec;41(6):2079-86

Mesh Tags

Substances

PMID: 23042038

search → result