Signaling from the Golgi: mechanisms and models for Golgi phosphoprotein 3-mediated oncogenesis.
Signaling from the Golgi: mechanisms and models for Golgi phosphoprotein 3-mediated oncogenesis.
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DOI：
10.1158/1078-0432.ccr-09-1695
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发表时间：
2010-04-15
期刊：
影响因子：
--
通讯作者：
Chin L
中科院分区：
文献类型：
--
作者：
Scott KL;Chin L
高尔基体磷蛋白3（Golgi Phosphoprotein 3，GOLPH 3，也称为GPP 34/GMx 33/MIDAS）代表了一类令人兴奋的参与囊泡运输的新癌蛋白。GOLPH 3由位于人类染色体5 p13上的基因编码，其在多种实体瘤类型中经常扩增，GOLPH 3最初被发现为定位于高尔基体的磷酸化蛋白。最近的功能、细胞生物学和生物化学分析表明，GOLPH 3可以作为癌蛋白发挥作用，通过增强哺乳动物雷帕霉素靶蛋白（mTOR）的活性来促进细胞转化和肿瘤生长，所述mTOR是一种丝氨酸/苏氨酸蛋白激酶，已知调节细胞生长、增殖和存活。虽然其在癌症中的确切作用模式仍有待阐明，但GOLPH 3参与蛋白质运输、受体再循环和糖基化的事实表明这些细胞过程与肿瘤发生的潜在联系。了解这些过程如何可能被解除管制，并有助于癌症的发病机制和药物反应将揭示新的途径，治疗干预。
Golgi Phosphoprotein 3 (GOLPH3, also known as GPP34/GMx33/MIDAS) represents an exciting new class of oncoproteins involved in vesicular trafficking. Encoded by a gene residing on human chromosome 5p13, which is frequently amplified in multiple solid tumor types, GOLPH3 was initially discovered as a phosphorylated protein localized to the Golgi apparatus. Recent functional, cell biological and biochemical analyses demonstrate that GOLPH3 can function as an oncoprotein to promote cell transformation and tumor growth by enhancing activity of the mammalian target of rapamycin (mTOR), a serine/threonine protein kinase known to regulate cell growth, proliferation, and survival. While its precise mode-of-action in cancer remains to be elucidated, the fact that GOLPH3 has been implicated in protein trafficking, receptor recycling and glycosylation points to potential links of these cellular processes to tumorigenesis. Understanding how these processes may be deregulated and contribute to cancer pathogenesis and drug response will uncover new avenues for therapeutic intervention.