Phosphorylation of Bcl2 and regulation of apoptosis

Ruvolo, Peter P.; Deng, Xingming; May, W. Stratford

doi:10.1038/sj.leu.2402090

Cited by 411 publications

(335 citation statements)

References 88 publications

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“…26,27 It is also notable that phosphorylation results in the activation of anti-apoptotic protein Bcl-2 and inactivation of proapoptotic protein BAD. 28,29 Importantly, we observed a significant reduction in Bcl-2 expression by 20% (MDA-MB-231) to 40% (MCF-7 and T-47D) after BEX2-KD (p < 0.03, Fig. 4a).…”

Section: Bex2 Regulates the Phosphorylation And Expression Of Bcl-2 Fmentioning

confidence: 73%

BEX2 regulates mitochondrial apoptosis and G1 cell cycle in breast cancer

Naderi¹,

Liu²,

Bennett³

2010

Intl Journal of Cancer

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We have recently demonstrated that BEX2 is differentially expressed in primary breast tumors and BEX2 expression is required for the Nerve Growth factor inhibition of ceramide-induced apoptosis in breast cancer. In this study we investigate the functional role of BEX2 in the survival and growth of breast cancer cells. We demonstrate that BEX2 downregulation induces mitochondrial apoptosis and sensitizes breast cancer cells to the pro-apoptotic effects of ceramide, doxorubicin and staurosporine. In addition, BEX2 overexpression protects the breast cancer cells against mitochondrial apoptosis. We show that this effect of BEX2 is mediated through the modulation of Bcl-2 protein family, which involves the positive regulation of anti-apoptotic member Bcl-2 and the negative regulation of pro-apoptotic members BAD, BAK1 and PUMA. Moreover, our data suggests that BEX2 expression is required for the normal cell cycle progression during G1 in breast cancer cells through the regulation of cyclin D1 and p21. To further support the significance of BEX2 in the pathogenesis of breast cancer we demonstrate that BEX2 overexpression is associated with a higher activation of the Bcl-2/NF-jB pathway in primary breast tumors. Furthermore, we show that BEX2 downregulation results in a higher expression and activity of protein phosphatase 2A. The modulation of protein phosphatase 2A, which is also known to mediate the cellular response to ceramide, provides a possible mechanism to explain the BEX2-mediated cellular effects. This study demonstrates that BEX2 has a significant role in the regulation of mitochondrial apoptosis and G1 cell cycle in breast cancer.

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Section: Bex2 Regulates the Phosphorylation And Expression Of Bcl-2 Fmentioning

confidence: 73%

BEX2 regulates mitochondrial apoptosis and G1 cell cycle in breast cancer

Naderi¹,

Liu²,

Bennett³

2010

Intl Journal of Cancer

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“…Bcl-2 family proteins are involved in the regulation of apoptosis and proposed to integrate signals from survivalinducing and death-promoting pathways [20,21]. To elucidate the effect of ALA on oocyte apoptosis, we analyzed the mRNA abundance of Bax, and Bcl-2 in oocyte after IVM.…”

Section: Discussionmentioning

confidence: 99%

Effect of Linolenic acid during in vitro maturation of ovine oocytes: embryonic developmental potential and mRNA abundances of genes involved in apoptosis

Veshkini

Asadi

Khadem

et al. 2015

J Assist Reprod Genet

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Purpose To study the effect of α-linolenic acid (ALA) on meiotic maturation, mRNA abundance of apoptosis-related (Bax and Bcl-2) molecules, and blastocyst formation in ovine oocytes. Methods A preliminary experiment was conducted to analyze the concentration of ALA in Bsmall^(≤2 mm) and Blarge( ≥6 mm) follicles using gas chromatography/mass spectrometry analysis. The concentration of ALA in small and large follicles was determined to be in a range of 75.4 to 125.7 μM,

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“…Theses include the negative selection of thymocytes (26), cytotoxic Tcell killing (27), and acute lymphoblastic leukaemia (28), etc. At the posttranscriptional level, the phosphorylation status of Bcl-2, dictated by various kinases and phosphatases, is key modulator of its stability and activity (29). Table 1 gives a few examples of both transcriptional and posttranslational regulation of the three subgroups of this family.…”

Section: Regulation Of Bcl-2 Family: Many Roads To Perditionmentioning

confidence: 99%

Bcl‐2 family proteins: The sentinels of the mitochondrial apoptosis pathway

2008

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SummaryBcl-2 family members are the arbiters of mitochondrial apoptotic pathway, which is conserved through evolution. The stoichiometry of pro-versus antiapoptotic Bcl-2 family members in the cell determines whether the cell lives or dies. This fine balance is regulated at the transcriptional or posttranslational level in response to various cellular cues. These signals are transmitted through the upstream molecules in the pathway, that is, the BH3-only molecules that results in the activation of the adaptor molecules, Bax and Bak, at the mitochondrial surface ensuing mitochondrial dysfunction and apoptosis. Understanding the activation process offers a great potential in the therapeutic intervention of many diseases such as cancer and autoimmune disorders.2008 IUBMB IUBMB Life, 60(6): [390][391][392][393][394][395][396][397] 2008

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Phosphorylation of Bcl2 and regulation of apoptosis

Cited by 411 publications

References 88 publications

BEX2 regulates mitochondrial apoptosis and G1 cell cycle in breast cancer

BEX2 regulates mitochondrial apoptosis and G1 cell cycle in breast cancer

Effect of Linolenic acid during in vitro maturation of ovine oocytes: embryonic developmental potential and mRNA abundances of genes involved in apoptosis

Bcl‐2 family proteins: The sentinels of the mitochondrial apoptosis pathway

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