PARP6, a mono(ADP-ribosyl) transferase and a negative regulator of cell proliferation, is involved in colorectal cancer development.
PARP6, a mono(ADP-ribosyl) transferase and a negative regulator of cell proliferation, is involved in colorectal cancer development.
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DOI：
10.3892/ijo.2012.1652
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发表时间：
2012-12
影响因子：
5.2
通讯作者：
H. Tuncel;Shinji Tanaka;S. Oka;S. Nakai;Ryuichiro Fukutomi;Mayumi Okamoto;T. Ota;H. Kaneko;M. Tatsuka;F. Shimamoto
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文献类型：
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作者：
H. Tuncel;Shinji Tanaka;S. Oka;S. Nakai;Ryuichiro Fukutomi;Mayumi Okamoto;T. Ota;H. Kaneko;M. Tatsuka;F. Shimamoto
聚（ADP-核糖）聚合酶（PARP）是一种介导蛋白质翻译后修饰的酶。根据催化活性，PARP 超家族的 17 个已知成员可分为三类：(i) 经典聚 (ADP-核糖) 聚合酶、(ii) 单 (ADP-核糖基) 转移酶和 (iii) 催化非活性成员。 PARP6属于单(ADP-核糖基)转移酶类，在这里我们发现PARP6是细胞增殖的负调节因子。 PARP6 在 HeLa 细胞中的强制表达会导致生长抑制，但 C 端缺失且缺乏催化结构域的 PARP6 突变体则没有效果。表达 PARP6 的细胞在 S 期积累，并且在表达具有 N 末端缺失、缺乏假定的调节域的 PARP6 突变体的细胞中观察到 S 期积累的程度更大。免疫组织化学分析显示，与低分化组织学的结直肠癌组织相比，在高分化结直肠癌组织中发现 PARP6 阳性的频率更高。此外，PARP6 阳性与 Ki-67 增殖指数呈负相关。 Kaplan-Meier分析显示PARP6阳性结直肠癌预后良好。基于这些结果，我们提出 PARP6 通过其在细胞周期控制中的作用充当肿瘤抑制因子。
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.