A myosin-Va tail fragment sequesters dynein light chains leading to apoptosis in melanoma cells.
A myosin-Va tail fragment sequesters dynein light chains leading to apoptosis in melanoma cells.
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DOI：
10.1038/cddis.2013.45
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发表时间：
2013-03-21
影响因子：
9
通讯作者：
Espreafico, E. M.
中科院分区：
文献类型：
--
作者：
Izidoro-Toledo, T. C.;Borges, A. C.;Araujo, D. D.;Leitao Mazzi, D. P. S.;Nascimento Junior, F. O.;Sousa, J. F.;Alves, C. P.;Paiva, A. P. B.;Trindade, D. M.;Patussi, E. V.;Peixoto, P. M.;Kinnally, K. W.;Espreafico, E. M.
以往的研究认为肌球蛋白Va通过动力蛋白轻链2（DLC 2）将促凋亡的Bmf隔离到肌动蛋白细胞骨架上来调节细胞凋亡。粘附损失或其他细胞骨架扰动将释放Bmf，使其能够结合并抑制促存活Bcl 2蛋白。在这里，我们证明了一个肌球蛋白-Va中间尾片段（MVaf）窝藏DLC 2的结合位点的过表达显着降低黑色素瘤细胞的活力。形态学和分子生物学变化，包括表面起泡、线粒体外膜透化、细胞色素C和Smac释放，以及caspase-9/-3激活和DNA片段化，表明黑色素瘤细胞死于凋亡。固定化MVaf与DLCs直接相互作用，但复合MVaf/DLCs不与Bmf相互作用。DLC 2的过表达减弱MVaf诱导的细胞凋亡。因此，我们认为，MVaf诱导细胞凋亡的隔离DLC 2和DLC 1，从而释放对敏化剂和激活剂BH 3-唯一的蛋白质BMF和Bim。缺乏Bim和Bmf或Bax和巴克的小鼠胚胎成纤维细胞（MEFs）比野生型MEFs对MVaf表达引起的细胞凋亡不敏感，加强了内在凋亡途径在这种反应中的假定作用。最后，MVaf表达减弱了小鼠B16-F10实体瘤的生长，这表明该肽可用作基础和翻译研究的促凋亡诱导工具。
Previous studies proposed that myosin-Va regulates apoptosis by sequestering pro-apoptotic Bmf to the actin cytoskeleton through dynein light chain-2 (DLC2). Adhesion loss or other cytoskeletal perturbations would unleash Bmf, allowing it to bind and inhibit pro-survival Bcl2 proteins. Here, we demonstrated that overexpression of a myosin-Va medial tail fragment (MVaf) harboring the binding site for DLC2 dramatically decreased melanoma cell viability. Morphological and molecular changes, including surface blebbing, mitochondrial outer membrane permeabilization, cytochrome-c and Smac release, as well as caspase-9/-3 activation and DNA fragmentation indicated that melanoma cells died of apoptosis. Immobilized MVaf interacted directly with DLCs, but complexed MVaf/DLCs did not interact with Bmf. Overexpression of DLC2 attenuated MVaf-induced apoptosis. Thus, we suggest that, MVaf induces apoptosis by sequestering DLC2 and DLC1, thereby unleashing the pair of sensitizer and activator BH3-only proteins Bmf and Bim. Murine embryonic fibroblasts (MEFs) lacking Bim and Bmf or Bax and Bak were less sensitive to apoptosis caused by MVaf expression than wild-type MEFs, strengthening the putative role of the intrinsic apoptotic pathway in this response. Finally, MVaf expression attenuated B16-F10 solid tumor growth in mice, suggesting that this peptide may be useful as an apoptosis-inducing tool for basic and translational studies.
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癌代谢中的葡萄糖转运蛋白。
影响因子：
3.4
作者：
Adekola K;Rosen ST;Shanmugam M
通讯作者：
Shanmugam M
Rab10 和肌球蛋白-Va 介导脂肪细胞中胰岛素刺激的 GLUT4 储存囊泡易位
DOI：
10.1083/jcb.201111091
发表时间：
2012-08-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
Chen Y;Wang Y;Zhang J;Deng Y;Jiang L;Song E;Wu XS;Hammer JA;Xu T;Lippincott-Schwartz J
通讯作者：
Lippincott-Schwartz J
影响因子：
10.5
作者：
Larribere, L;Hilmi, C;Bertolotto, C
通讯作者：
Bertolotto, C
影响因子：
7.8
作者：
Espreafico, E M;Cheney, R E;Matteoli, M;Nascimento, A A;De Camilli, P V;Larson, R E;Mooseker, M S
通讯作者：
Mooseker, M S
DOI：
10.1073/pnas.0438011100
发表时间：
2003-03-04
影响因子：
11.1
作者：
Lei, K;Davis, RJ
通讯作者：
Davis, RJ