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癌蛋白GOLPH3在胞质分裂过程中收缩环组装和膜运输中的作用。

The roles of the oncoprotein GOLPH3 in contractile ring assembly and membrane trafficking during cytokinesis.

作者信息

Sechi Stefano, Frappaolo Anna, Belloni Giorgio, Giansanti Maria Grazia

机构信息

Istituto di Biologia e Patologia molecolari del CNR, Università Sapienza di Roma, Piazzale Aldo Moro 5, 00185 Roma, Italy.

†Dipartimento di Biologia e Biotecnologie, Università Sapienza di Roma, Piazzale Aldo Moro 5, 00185 Roma, Italy.

出版信息

Biochem Soc Trans. 2015 Feb;43(1):117-21. doi: 10.1042/BST20140264.

Abstract

Cytokinesis is an intricate process that requires an intimate interplay between actomyosin ring constriction and plasma membrane remodelling at the cleavage furrow. However, the molecular mechanisms involved in coupling the cytoskeleton dynamics with vesicle trafficking during cytokinesis are poorly understood. The highly conserved Golgi phosphoprotein 3 (GOLPH3), functions as a phosphatidylinositol 4-phosphate (PI4P) effector at the Golgi. Recent studies have suggested that GOLPH3 is up-regulated in several cancers and is associated with poor prognosis and more aggressive tumours. In Drosophila melanogaster, GOLPH3 localizes at the cleavage furrow of dividing cells, is required for successful cytokinesis and acts as a key molecule in coupling phosphoinositide (PI) signalling with actomyosin ring dynamics. Because cytokinesis failures have been linked with pre-malignant disease and cancer, the novel connection between GOLPH3 and cytokinesis imposes new fields of investigation in cancer biology and therapy.

摘要

胞质分裂是一个复杂的过程,需要肌动球蛋白环收缩与分裂沟处的质膜重塑之间密切相互作用。然而,在胞质分裂过程中,将细胞骨架动力学与囊泡运输耦合起来的分子机制仍知之甚少。高度保守的高尔基体磷蛋白3(GOLPH3)在高尔基体中作为磷脂酰肌醇4-磷酸(PI4P)效应器发挥作用。最近的研究表明,GOLPH3在几种癌症中上调,与预后不良和更具侵袭性的肿瘤相关。在黑腹果蝇中,GOLPH3定位于分裂细胞的分裂沟,是成功进行胞质分裂所必需的,并且在将磷酸肌醇(PI)信号与肌动球蛋白环动力学耦合中起关键分子的作用。由于胞质分裂失败与癌前疾病和癌症有关,GOLPH3与胞质分裂之间的新联系为癌症生物学和治疗带来了新的研究领域。

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