PNUTS Functions as a Proto-Oncogene by Sequestering PTEN
PNUTS Functions as a Proto-Oncogene by Sequestering PTEN
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DOI：
10.1158/0008-5472.can-12-1394
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发表时间：
2013-01-01
期刊：
影响因子：
11.2
通讯作者：
Maddika, Subbareddy
中科院分区：
文献类型：
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作者：
Kavela, Sridhar;Shinde, Swapnil R.;Maddika, Subbareddy
PTEN是一个明确的肿瘤抑制基因，它拮抗PI3K/Akt通路，调节一系列细胞过程，如生存、生长、运动、侵袭和血管生成。虽然PTEN的功能已经得到了广泛的研究，但它在正常和疾病条件下的活性调节仍然不完全清楚。在本研究中，我们鉴定了蛋白磷酸酶-1核靶向亚基PNUTS(PPP1R10)是一种与PTEN相关的蛋白。PNUTS直接与PTEN的脂结合结构域(C2结构域)相互作用，并将其隔离在细胞核内。PNUTS的缺失以一种依赖PTEN的方式导致细胞凋亡增加和细胞增殖减少。与匹配的正常组织相比，PNUTS在某些肿瘤组织中的表达升高。总之，我们的研究揭示了PNUTS是一种新的PTEN调节因子和可能的癌基因。巨蟹座；73(1)；205-14。(C)2012年AACR。
PTEN is a well-defined tumor suppressor gene that antagonizes the PI3K/Akt pathway to regulate a multitude of cellular processes, such as survival, growth, motility, invasiveness, and angiogenesis. While the functions of PTEN have been studied extensively, the regulation of its activity during normal and disease conditions still remains incompletely understood. In this study, we identified the protein phosphatase-1 nuclear targeting subunit PNUTS (PPP1R10) as a PTEN-associated protein. PNUTS directly interacted with the lipid-binding domain (C2 domain) of PTEN and sequestered it in the nucleus. Depletion of PNUTS leads to increased apoptosis and reduced cellular proliferation in a PTEN-dependent manner. PNUTS expression was elevated in certain cancers compared with matched normal tissues. Collectively, our studies reveal PNUTS as a novel PTEN regulator and a likely oncogene. Cancer Res; 73(1); 205-14. (C) 2012 AACR.