The following BBC3 reagents supplied by CUSABIO are manufactured under a strict quality control system. Multiple applications have been validated and solid technical support is offered.

BBC3 Antibodies

BBC3 Antibodies for Homo sapiens (Human)

BBC3 Proteins

BBC3 Proteins for Rattus norvegicus (Rat)

BBC3 Proteins for Mus musculus (Mouse)

BBC3 Proteins for Homo sapiens (Human)

BBC3 Background

The BBC3 gene encodes for Bcl-2-binding component 3 (BBC3) protein in humans that belongs to one type of PUMA (p53 upregulated modulator of apoptosis) identified through yeast two-hybrid screening [1]. BBC3 gene is a novel BH3-only protein-encoding gene isolated by screening a human lymphocyte cDNA library [1], and the other two are cDNA clones encoding Bik and Bad, previously identified BH3-only proteins that bind to Bcl-2. BBC3 protein contains two functional domains: the BH3 domain that is required for interactions with Bcl-2-like proteins such as Bcl-2 & Bcl-XL [2][3] and a C-terminal mitochondria-localization signal (MLS) domain [4]. Jia-wen Han et al. demonstrated that BBC3 functions to promote apoptosis in a mechanistically similar fashion to previously characterized BH3-only proteins Bik and Bad by observing the BH3-dependent dimerization and pro-apoptotic activities of BBC3 [5]. The mechanism process is that upon activation, the BH3-only proteins can activate BAX and BAK, thereby triggering cytochrome c release and apoptosis. They also indicated that BBC3 is a direct transcriptional target of p53 because of p53 transactivated BBC3 through consensus p53 binding sites within the BBC3 promoter region [5]. Additionally, BBC3 mRNA was induced by p53-independent apoptotic stimuli, including dexamethasone treatment of thymocytes and serum deprivation of tumor cells [5]. Growth factors with anti-apoptotic activity inhibit BBC3 expression [5]. The inhibition of BBC3 expression mediated by the IGF-1 receptor may provide an additional, sustained anti-apoptotic signal by reducing the effective levels of BH3 in cells. Dysregulation of the mechanisms that normally control the transcription of BBC3 may contribute to the evolution and/or survival of tumor cells. The loss of p53 function may prevent the activation of BBC3 that would normally follow DNA damage.

[1] Han J, Flemington C, et al. Expression of bbc3, a pro-apoptotic BH3-only gene, is regulated by diverse cell death and survival signals [J]. Proc Natl Acad Sci USA 98: 11318-11323.
[2] Nakano K, Vousden KH. PUMA, a novel proapoptotic gene, is induced by p53 [J]. Mol Cell, 2001, 7: 683-694.
[3] Yu J, Zhang L, et al. PUMA induces the rapid apoptosis of colorectal cancer cells [J]. Mol Cell, 2001, 7: 673-682.
[4] Yu J, Wang Z, et al. PUMA mediates the apoptotic response to p53 in colorectal cancer cells [J]. Proc Natl Acad Sci USA, 2003, 100: 1931-1936.
[5] Jia-wen Han, Cathy Flemington, et al. Expression of bbc3, a pro-apoptotic BH3-only gene, is regulated by diverse cell death and survival signals [J]. PNAS September 25, 2001 98 (20) 11318-11323.

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