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


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Tuncel H. , Tanaka S., Oka S., Nakai S., Fukutomi R., Okamoto M., ...Daha Fazla

International Journal of Oncology, cilt.41, ss.2079-2086, 2012 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 41 Konu: 6
  • Basım Tarihi: 2012
  • Doi Numarası: 10.3892/ijo.2012.1652
  • Dergi Adı: International Journal of Oncology
  • Sayfa Sayıları: ss.2079-2086

Özet

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.