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Gene Review

Bbc3  -  BCL2 binding component 3

Mus musculus

Synonyms: Bcl-2-binding component 3, PUMA, PUMA/JFY1, Puma, p53 up-regulated modulator of apoptosis
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Disease relevance of Bbc3

  • We have recently shown that Puma is required for cardiac cell death upon ischemia/reperfusion of mouse hearts [1].
  • OBJECTIVE: Puma (p53-upregulated modulator of apoptosis), a proapoptotic BH3-only member of the Bcl-2 protein family, has been implicated in the pathomechanism of several diseases, including cancer, AIDS, and ischemic brain disease [1].
  • Our study thus establishes Puma as an essential mediator of cardiomyocyte death upon I/R injury and offers a novel therapeutic target to limit cell loss in ischemic heart disease [2].

High impact information on Bbc3


Biological context of Bbc3

  • In particular, the absence of Puma or Bim renders thymocytes and mature lymphocytes refractory to varying degrees to death induced in vitro by growth factor withdrawal, DNA damage, or glucocorticoids [6].

Anatomical context of Bbc3

  • This Bim-independent death pathway is at least in part regulated by Puma, as shown by analysis of puma-/- and noxa-/- T cells [7].
  • In normal cells, and in precancerous B cells of E micro -myc transgenic mice, this apoptotic response is associated with the suppression of the antiapoptotic regulators Bcl-2 and Bcl-X(L) and with the concomitant induction of Puma, a proapoptotic BH3-only protein [8].
  • Most importantly, cardiac myocytes acquired resistance to ER stress-induced apoptosis if Puma expression was downregulated by adenoviral delivery of shRNA or eliminated by targeted deletion in knockout mice [1].
  • Since ischemia/reperfusion is also associated with endoplasmic reticulum (ER) stress, in the present study we investigated whether Puma contributes to the ER stress-dependent component of cardiomyocyte apoptosis [1].

Associations of Bbc3 with chemical compounds


Regulatory relationships of Bbc3


Other interactions of Bbc3


Analytical, diagnostic and therapeutic context of Bbc3


  1. PUMA is critical for neonatal cardiomyocyte apoptosis induced by endoplasmic reticulum stress. Nickson, P., Toth, A., Erhardt, P. Cardiovasc. Res. (2007) [Pubmed]
  2. Targeted deletion of Puma attenuates cardiomyocyte death and improves cardiac function during ischemia-reperfusion. Toth, A., Jeffers, J.R., Nickson, P., Min, J.Y., Morgan, J.P., Zambetti, G.P., Erhardt, P. Am. J. Physiol. Heart Circ. Physiol. (2006) [Pubmed]
  3. FOXO3a-dependent regulation of Puma in response to cytokine/growth factor withdrawal. You, H., Pellegrini, M., Tsuchihara, K., Yamamoto, K., Hacker, G., Erlacher, M., Villunger, A., Mak, T.W. J. Exp. Med. (2006) [Pubmed]
  4. Puma cooperates with Bim, the rate-limiting BH3-only protein in cell death during lymphocyte development, in apoptosis induction. Erlacher, M., Labi, V., Manzl, C., B??ck, G., Tzankov, A., H??cker, G., Michalak, E., Strasser, A., Villunger, A. J. Exp. Med. (2006) [Pubmed]
  5. The limited role of NH2-terminal c-Jun phosphorylation in neuronal apoptosis: identification of the nuclear pore complex as a potential target of the JNK pathway. Besirli, C.G., Wagner, E.F., Johnson, E.M. J. Cell Biol. (2005) [Pubmed]
  6. BH3-only proteins Puma and Bim are rate-limiting for gamma-radiation- and glucocorticoid-induced apoptosis of lymphoid cells in vivo. Erlacher, M., Michalak, E.M., Kelly, P.N., Labi, V., Niederegger, H., Coultas, L., Adams, J.M., Strasser, A., Villunger, A. Blood (2005) [Pubmed]
  7. The NF-kappaB regulator Bcl-3 and the BH3-only proteins Bim and Puma control the death of activated T cells. Bauer, A., Villunger, A., Labi, V., Fischer, S.F., Strasser, A., Wagner, H., Schmid, R.M., Häcker, G. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  8. c-Myc augments gamma irradiation-induced apoptosis by suppressing Bcl-XL. Maclean, K.H., Keller, U.B., Rodriguez-Galindo, C., Nilsson, J.A., Cleveland, J.L. Mol. Cell. Biol. (2003) [Pubmed]
  9. Mutually exclusive subsets of BH3-only proteins are activated by the p53 and c-Jun N-terminal kinase/c-Jun signaling pathways during cortical neuron apoptosis induced by arsenite. Wong, H.K., Fricker, M., Wyttenbach, A., Villunger, A., Michalak, E.M., Strasser, A., Tolkovsky, A.M. Mol. Cell. Biol. (2005) [Pubmed]
  10. BH3-only proapoptotic Bcl-2 family members Noxa and Puma mediate neural precursor cell death. Akhtar, R.S., Geng, Y., Klocke, B.J., Latham, C.B., Villunger, A., Michalak, E.M., Strasser, A., Carroll, S.L., Roth, K.A. J. Neurosci. (2006) [Pubmed]
  11. Expression of bbc3, a pro-apoptotic BH3-only gene, is regulated by diverse cell death and survival signals. Han, J., Flemington, C., Houghton, A.B., Gu, Z., Zambetti, G.P., Lutz, R.J., Zhu, L., Chittenden, T. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  12. Bim and Bad mediate imatinib-induced killing of Bcr/Abl+ leukemic cells, and resistance due to their loss is overcome by a BH3 mimetic. Kuroda, J., Puthalakath, H., Cragg, M.S., Kelly, P.N., Bouillet, P., Huang, D.C., Kimura, S., Ottmann, O.G., Druker, B.J., Villunger, A., Roberts, A.W., Strasser, A. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  13. Puma is an essential mediator of p53-dependent and -independent apoptotic pathways. Jeffers, J.R., Parganas, E., Lee, Y., Yang, C., Wang, J., Brennan, J., MacLean, K.H., Han, J., Chittenden, T., Ihle, J.N., McKinnon, P.J., Cleveland, J.L., Zambetti, G.P. Cancer Cell (2003) [Pubmed]
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