CIP2A在人类恶性肿瘤中抑制蛋白磷酸酶2A（PP2A）。
CIP2A inhibits PP2A in human malignancies.
作者信息
Junttila Melissa R, Puustinen Pietri, Niemelä Minna, Ahola Raija, Arnold Hugh, Böttzauw Trine, Ala-aho Risto, Nielsen Christina, Ivaska Johanna, Taya Yoichi, Lu Shi-Long, Lin Shujun, Chan Edward K L, Wang Xiao-Jing, Grènman Reidar, Kast Juergen, Kallunki Tuula, Sears Rosalie, Kähäri Veli-Matti, Westermarck Jukka
机构信息
Centre for Biotechnology, University of Turku and Abo Akademi University, 20520 Turku, Finland.
出版信息
Cell. 2007 Jul 13;130(1):51-62. doi: 10.1016/j.cell.2007.04.044.
Inhibition of protein phosphatase 2A (PP2A) activity has been identified as a prerequisite for the transformation of human cells. However, the molecular mechanisms by which PP2A activity is inhibited in human cancers are currently unclear. In this study, we describe a cellular inhibitor of PP2A with oncogenic activity. The protein, designated Cancerous Inhibitor of PP2A (CIP2A), interacts directly with the oncogenic transcription factor c-Myc, inhibits PP2A activity toward c-Myc serine 62 (S62), and thereby prevents c-Myc proteolytic degradation. In addition to its function in c-Myc stabilization, CIP2A promotes anchorage-independent cell growth and in vivo tumor formation. The oncogenic activity of CIP2A is demonstrated by transformation of human cells by overexpression of CIP2A. Importantly, CIP2A is overexpressed in two common human malignancies, head and neck squamous cell carcinoma (HNSCC) and colon cancer. Thus, our data show that CIP2A is a human oncoprotein that inhibits PP2A and stabilizes c-Myc in human malignancies.
蛋白磷酸酶2A（PP2A）活性的抑制已被确定为人类细胞转化的一个先决条件。然而，目前尚不清楚在人类癌症中PP2A活性被抑制的分子机制。在本研究中，我们描述了一种具有致癌活性的PP2A细胞抑制剂。该蛋白被命名为PP2A癌性抑制剂（CIP2A），它直接与致癌转录因子c-Myc相互作用，抑制PP2A对c-Myc丝氨酸62（S62）的活性，从而防止c-Myc的蛋白水解降解。除了在稳定c-Myc方面的作用外，CIP2A还促进不依赖贴壁的细胞生长和体内肿瘤形成。CIP2A的致癌活性通过过表达CIP2A对人类细胞的转化得以证明。重要的是，CIP2A在两种常见的人类恶性肿瘤——头颈部鳞状细胞癌（HNSCC）和结肠癌中过表达。因此，我们的数据表明CIP2A是一种人类癌蛋白，它在人类恶性肿瘤中抑制PP2A并稳定c-Myc。
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