生物
细胞周期蛋白D1
细胞生物学
细胞周期蛋白D
细胞凋亡
细胞周期蛋白
程序性细胞死亡
热休克蛋白
周期素
细胞周期蛋白B
线粒体
癌症研究
细胞周期
生物化学
基因
作者
Gaël Roué,Vianney Pichereau,Hubert Lincet,Dolors Colomer,Brigitte Sola
出处
期刊:Oncogene
[Springer Nature]
日期:2008-04-28
卷期号:27 (36): 4909-4920
被引量:51
摘要
Cyclin D1 is a key regulator of cell proliferation. It also controls other aspects of the cell fate, such as cellular senescence, apoptosis and tumourigenesis. We used B-lymphoid cell lines producing cyclin D1 to investigate the role of this protein in B-cell lymphomas and leukaemias. Constitutive low levels of cyclin D1 had no effect per se on cell proliferation, but conferred resistance to various apoptotic stimuli in B cells. Activation of the pro-apoptotic protein, Bax, was reduced and mitochondrial permeabilization and phosphatidylserine exposure following cytokine withdrawal were delayed in cyclin D1-producing cells. Proteomic analysis showed that the presence of cyclin D1 led to intracellular accumulation of various molecular chaperones. The chaperone, heat shock protein (Hsp)70, bound to both Bax and the mitochondrial apoptosis inducing factor following cytokine withdrawal, and impeded inhibitors of κB (IκB)-mediated inhibition of nuclear factor-κB anti-apoptotic signalling. Impairment of Hsp70 activity—using a pharmacological Hsp inhibitor or transfecting cells with an Hsp70-blocking antibody—restored the cellular response to mitochondrial apoptosis triggering. Thus, constitutive de-novo cyclin D1 production in B cells delays commitment to apoptosis by inducing Hsp70 chaperoning activity on pre- and post-mitochondrial pro-apoptotic factors.
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