Cytosol-to-membrane redistribution of Bax and Bcl-X-L during apoptosis
Cytosol-to-membrane redistribution of Bax and Bcl-X-L during apoptosis
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DOI：
10.1073/pnas.94.8.3668
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发表时间：
1997-04-15
影响因子：
11.1
通讯作者：
Youle, RJ
中科院分区：
文献类型：
--
作者：
Hsu, YT;Wolter, KG;Youle, RJ
Bcl-2、Bcl-X-L和fax是Bcl-2家族的成员，在细胞凋亡的调节中起关键作用。这些蛋白质被认为是膜结合的，并且已经提出它们经历同源二聚化和异源二聚化的能力来调节细胞凋亡。在此，我们报告，在小鼠胸腺细胞，Bcl-2是专门的膜结合，而Bax主要存在于胞质溶胶和Bcl-X-L是目前在可溶性和膜结合的形式。地塞米松或γ射线照射诱导小鼠胸腺细胞凋亡使Bax和Bcl-X-L的亚细胞位置从可溶性形式转变为膜结合形式。在HL-60白血病细胞中，星形孢菌素诱导凋亡后，观察到Bax从胞浆到膜的定位发生类似的变化。放线菌酮抑制细胞凋亡抑制地塞米松处理诱导的胸腺细胞中Bax和Bcl-X-L从胞浆进入膜的运动。这些运动可能代表了该家族成员调节细胞凋亡的途径中的重要步骤。
Bcl-2, Bcl-X-L, and fax are members of the Bcl-2 family that play key roles in the regulation of apoptosis. These proteins are believed to be membrane bound and their ability to undergo both homodimerization and heterodimerization has been proposed to regulate apoptosis. Herein we report that in murine thymocytes, Bcl-2 is exclusively membrane-bound, whereas Bax is present predominantly in the cytosol and Bcl-X-L is present in both soluble and membrane-bound forms. Induction of apoptosis in murine thymocytes by dexamethasone or gamma-irradiation shifts the subcellular locations of Bax and Bcl-X-L from soluble to membrane-bound forms. A similar shift in the localization of Bax from the cytosol to membranes was observed in HL-60 leukemia cells upon induction of apoptosis by staurosporine. Inhibition of apoptosis with cycloheximide inhibits the movement of Bax and Bcl-X-L in thymocytes from the cytosol into membranes induced by dexamethasone treatment. These movements may represent an important step in the pathway by which members of this family regulate apoptosis.