PARP6, a mono(ADP-ribosyl) transferase and a negative regulator of cell proliferation, is involved in colorectal cancer development
| Autor: | Shiro Oka, Ryuichiro Fukutomi, Takahide Ota, Handan Tuncel, Mayumi Okamoto, Shiro Nakai, Shinji Tanaka, Fumio Shimamoto, Hiroshi Kaneko, Masaaki Tatsuka |
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| Rok vydání: | 2012 |
| Předmět: |
Cancer Research
Proliferation index Poly ADP ribose polymerase Molecular Sequence Data Cell Gene Expression Biology S Phase HeLa Cell Line Tumor medicine Humans Amino Acid Sequence Cell Proliferation Neoplasm Staging ADP Ribose Transferases Oncogene Cell growth Cell cycle Prognosis biology.organism_classification Molecular biology Cell Transformation Neoplastic medicine.anatomical_structure Oncology Cell culture Poly(ADP-ribose) Polymerases Colorectal Neoplasms Sequence Alignment |
| Zdroj: | International Journal of Oncology. 41:2079-2086 |
| ISSN: | 1791-2423 1019-6439 |
| DOI: | 10.3892/ijo.2012.1652 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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