BAD Research Reagents

BAD Background

Bcl2-associated agonist of cell death (BAD) is a protein in humans that is encoded by a BAD gene. BAD belongs to a member of the BH3 ( Bcl-2 homology 3)-only family ^[1], a subfamily of the Bcl-2 family. BAD only contains the BH3 domain required for its induction of apoptosis ^[2][3] and lacks a C-terminal transmembrane domain for the outer mitochondrial membrane ^[4]. The sensitizer BH3-only protein BAD is abundantly expressed in many epithelial cells and acts in inducing apoptotic signals ^[2][5]. The pro-apoptotic functions of BAD are directly mediated through interaction of BAD with Bcl-2 and Bcl-xl via the BH3 domain of BAD and through subsequent ablation of the pro-apoptotic activity of Bcl-2 and Bcl-xl ^[3][6]. This ablation allows activation of downstream molecules, such as Bax and Bak, to induce the cell to apoptosis ^[7][8]. Li Jiang et al. demonstrated that BAD overexpression in non-small cell lung cancer (NSCLC) led cancer cells to undergo apoptosis through a mitochondrial pathway which is independent of Bax, Bcl-2, and Bcl-xl expression levels ^[9]. In addition to regulating apoptosis, BAD proteins also are associated with cell proliferation. But the effect of BAD on cell proliferation may be cell- type-specific. For example, increased BAD expression promotes the proliferation of prostate cancer cells ^[10]. And previous studies have reported that BAD contributes to tumorigenesis in several cancers ^[11-13]. Whereas, cell growth is inhibited by BAD overexpression in breast cancer cell MCF7 ^[14], lung adenocarcinoma cell line A549 ^[15], and NSCLC ^[9]. It suggests that BAD is a novel potential target for tumor interventions.

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[2] Zha J, Harada H, et al. Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14-3-3 not BCL-XL [J]. Cell, 1996, 87: 619-628.
[3] Zha J, Harada H, et al. BH3 domain of BAD is required for heterodimerization [J]. J. Biol. Chem. 1997, 272: 24101-24104.
[4] K Wang, X M Yin, et al. BID: A Novel BH3 Domain-Only Death Agonist [J]. Genes Dev, 1996, 10 (22), 2859-69.
[5] Kitada S, Krajewska M, et al. Expression and location of pro-apoptotic Bcl-2 family protein BAD in normal human tissues and tumor cell lines Am [J]. J. Pathol. 1998, 152: 51–61.
[6] Yang E, Zha J, et al. Bad, a heterodimeric partner for Bcl-XL and Bcl-2, displaces Bax and promotes cell death [J]. Cell, 1995, 80: 285-291.
[7] Adams JM, Cory S. The Bcl-2 apoptotic switch in cancer development and therapy [J]. Oncogene. 2007 Feb 26; 26(9):1324-37.
[8] Sommer P, Cowen RL, et al. Glucocorticoid receptor over-expression promotes human small cell lung cancer apoptosis in vivo and thereby slows tumor growth [J]. Endocr Relat Cancer. 2010 Mar; 17 (1):203-13.
[9] Li Jiang, Man Luo, et al. BAD overexpression inhibits cell growth and induces apoptosis via mitochondrial-dependent pathway in non-small cell lung cancer [J]. Cancer Cell Int. 2013; 13: 53.
[10] Smith AJ, Karpova Y, et al. Expression of the Bcl-2 protein BAD promotes prostate cancer growth [J]. PLoS One. 2009 Jul 13; 4(7):e6224.
[11] Sinicrope FA, Rego RL, et al. Proapoptotic Bad and Bid protein expression predict survival in stages II and III colon cancers [J]. Clin Cancer Res. 2008 Jul 1; 14(13):4128-33.
[12] Al-Bazz YO, Underwood JC, et al. Prognostic significance of Akt, phospho-Akt and BAD expression in primary breast cancer [J]. Eur J Cancer. 2009 Mar; 45(4):694-704.
[13] Marchion DC, Cottrill HM, et al. BAD phosphorylation determines ovarian cancer chemosensitivity and patient survival [J]. Clin Cancer Res. 2011 Oct 1; 17(19):6356-66.  
[14] Fernando R, Foster JS, et al. Breast cancer cell proliferation is inhibited by BAD: regulation of cyclin D1 [J]. J Biol Chem. 2007 Sep 28; 282(39):28864-73.
[15] Huang N, Zhu J, et al. Overexpression of Bcl-2-associated death inhibits A549 cell growth in vitro and in vivo [J]. Cancer Biother Radiopharm. 2012 Mar; 27(2):164-8.