最近,Michigan州立大学和Van Andel研究所的研究人员从事的人类细胞繁殖的研究,其研究报告或许能使科学家距离找到癌症的“关闭”开关更近一步。该研究报告发表在最近出版的《生物化学杂志》(Journal of Biological Chemistry,JBC)上。
癌细胞能够无限地分裂增殖,并能在机体中发生转移,在这个过程中,癌细胞的形状发生改变。研究人员DeWard及其同事发现一种命名为formins的蛋白质在细胞分裂和移动时能够决定细胞的形状,并发现了细胞分裂时formins的调节机制。
目前,针对这类蛋白质如何启动相关功能有大量的相关研究,但如何关闭这类蛋白质家族的功能还不清楚。因此,该课题的研究人员提供了旨在找到能特异性关闭无限增殖的癌细胞的分子机制。
DeWard说,虽然关闭细胞分裂过程并不意味着能够阻止癌症的发生,但了解相关分子机制能够使研究人员找到更好地控制癌症发生的途径。(生物谷Bioon.com)
生物谷推荐原始出处:
J. Biol. Chem., Vol. 284, Issue 30, 20061-20069, July 24, 2009
Ubiquitin-mediated Degradation of the Formin mDia2 upon Completion of Cell Division*
Aaron D. DeWard and Arthur S. Alberts1
From the From the Laboratory of Cell Structure and Signal Integration, Van Andel Research Institute, Grand Rapids, Michigan 49503 and , the Program in Cell and Molecular Biology, Michigan State University, East Lansing, Michigan 48824
ABSTRACT
Formins assemble non-branched actin filaments and modulate microtubule dynamics during cell migration and cell division. At the end of mitosis formins contribute to the generation of actin filaments that form the contractile ring. Rho small GTP-binding proteins activate mammalian diaphanous-related (mDia) formins by directly binding and disrupting an intramolecular autoinhibitory mechanism. Although the Rho-regulated activation mechanism is well characterized, little is known about how formins are switched off. Here we reveal a novel mechanism of formin regulation during cytokinesis based on the following observations; 1) mDia2 is degraded at the end of mitosis, 2) mDia2 is targeted for disposal by post-translational ubiquitin modification, 3) forced expression of activated mDia2 yields binucleate cells due to failed cytokinesis, and 4) the cytokinesis block is dependent upon mDia2-mediated actin assembly as versions of mDia2 incapable of nucleating actin but that still stabilize microtubules have no effect on cytokinesis. We propose that the tight control of mDia2 expression and ubiquitin-mediated degradation is essential for the completion of cell division. Because of the many roles for formins in cell morphology, we discuss the relevance of mDia protein turnover in other processes where ubiquitin-mediated proteolysis is an essential component.