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

Tuncel,Handan; Tanaka,Shinji; Oka,Shiro; Nakai,Shiro; Fukutomi,Ryuichiro; Okamoto,Mayumi; Ota,Takahide; Kaneko,Hiroshi; Tatsuka,Masaaki; Shimamoto,Fumio

doi:10.3892/ijo.2012.1652

December 2012 Volume 41 Issue 6

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December 2012 Volume 41 Issue 6

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Article

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

Authors:
- Handan Tuncel
- Shinji Tanaka
- Shiro Oka
- Shiro Nakai
- Ryuichiro Fukutomi
- Mayumi Okamoto
- Takahide Ota
- Hiroshi Kaneko
- Masaaki Tatsuka
- Fumio Shimamoto
View Affiliations / Copyright

Affiliations: Department of Biophysics, Cerrahpasa Medical Faculty, Istanbul University, Istanbul 34303, Turkey, Department of Endoscopy, Hiroshima University Hospital, Minami-ku, Hiroshima 734-8553, Japan, Department of Surgery, Hiroshima Memorial Hospital, Naka-ku, Hiroshima 730-0802, Japan, Department of Life Sciences, Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, Shoubara, Hiroshima 727-0023, Japan, Department of Life Sciences, Medical Research Institute, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan, Department of Health Sciences, Faculty of Human Culture and Science, Prefectural University of Hiroshima, Minami-ku, Hiroshima 734-8558, Japan
Pages: 2079-2086
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Published online on: October 4, 2012

https://doi.org/10.3892/ijo.2012.1652
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Abstract

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.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

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

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Abstract

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