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Gene Review

BBC3  -  BCL2 binding component 3

Homo sapiens

Synonyms: JFY-1, JFY1, PUMA
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Disease relevance of BBC3


High impact information on BBC3

  • Bim and Puma bind all the pro-survival proteins, whereas others, such as Noxa and Bad, engage distinct subsets and exhibit complementary killing [5].
  • Within the Bcl-2 family, distinct apoptogenic BH3-only members like Bid, Bim, and Puma appear to function in specific cell death pathways [6].
  • In contrast, Puma is considered the key mediator of p53-induced apoptosis [7].
  • Macroarrays led to the identification of several Env-elicited, p53-dependent proapoptotic transcripts, in particular Puma, a proapoptotic "BH3-only" protein from the Bcl-2 family known to activate Bax/Bak [8].
  • Moreover, circulating CD4+ lymphocytes from untreated, HIV-1-infected donors contained enhanced amounts of Puma protein, and these elevated Puma levels dropped upon antiretroviral therapy [8].

Chemical compound and disease context of BBC3

  • It has been reported that all major chlamydial species can inhibit host cell apoptosis and the Chlamydia trachomatis antiapoptotic activity is correlated with inhibition of activation of the proapoptotic multidomain Bcl-2 proteins Bax and Bak and degradation of BH3-only domain Bcl-2 proteins such as Puma [9].
  • Inadvertent ingestion of thiafentanil oxalate by a captive adult female mountain lion (Puma concolor) caused a prolonged clinical syndrome that included sedation and depression, muscle tension, and myopathy that was incompletely antagonized by naltrexone HCl [10].

Biological context of BBC3

  • Finally we demonstrated that BBC3 alone is sufficient to induce cell death in the 4-HPR-sensitive and resistant NB cell lines, and that siRNA against BBC3 significantly decreases apoptosis induced by 4-HPR [1].
  • Their binding sites were mapped to BH3 (Bcl-2 homology) domain of Puma and BH1 domain of Mcl-1, respectively [11].
  • In cells infected with a Chlamydia trachomatis L2 strain, Bim, Puma, and Bad were degraded with similar kinetics, and the degradation of all three was blocked by inhibition of the proteasome [12].
  • In contrast, parental 697 cells underwent typical apoptosis with up-regulation of Puma and Noxa proteins, followed by cytochrome c release and caspase-3/7 activation after treatment with topoisomerase inhibitor in the presence or absence of BSO [13].
  • Notably, we showed that proteasome-mediated down-regulation of Puma and Noxa proteins occurs in 697-Bcl-2 cells after treatment with BSO plus topoisomerase inhibitor, although there is an increase in the protein levels of p53 in these 697-Bcl-2 cells [13].

Anatomical context of BBC3

  • Furthermore, the induction of BBC3 was associated with the sensitivity to this agent in the cell lines tested [1].
  • Mcl-1 and Puma was shown to colocalize at the mitochondria by immunostaining [11].
  • Here we reported that myeloid cell leukemia-1 (Mcl-1), an anti-apoptotic member of the Bcl-2 family with a rapid turnover rate, interacts with Puma [11].
  • In normal cells, Puma but not Noxa induces mitochondrial outer membrane permeabilization (MOMP), and this function is mediated in part by a pathway that involves calcium release from the endoplasmic reticulum (ER) and the subsequent caspase activation [14].
  • Interestingly, although mTOR activation and Puma induction were observed in dying syncytia and neurons, IkB phosphorylation and TG2 up-regulation were only found in syncytia [15].

Associations of BBC3 with chemical compounds

  • Among a panel of p53 target genes tested by quantitative PCR, the gene showing the largest defect in induction by 5FU was BBC3 (PUMA), which was induced 4-fold by wild type p53 and 2-fold by the N6A mutant [16].
  • As shown recently, this inhibition is in part explained by the proteolytic degradation of the proapoptotic Bcl-2 family members (BH3-only proteins) Bim, Puma, and Bad upon chlamydial infection [12].
  • In adriamycin-treated BALB/3T3 cells, the down-shift in temperature from 37 degrees C to 32 degrees C increased the Bcl-xL protein level and decreased the mRNA level of Puma and mitochondrial translocation of Bax, suppressing caspase-9-mediated apoptosis [17].
  • Treatment of CLL cells with fludarabine induced only the proapoptotic genes Bax and Puma in a p53-dependent manner [3].
  • Moreover, inhibition of the p53 abrogated the induction of Puma and promotion of apoptosis due to 6-hydroxydopamine treatments [18].

Other interactions of BBC3

  • Two DNA damage-related pro-apoptotic proteins, Puma and Noxa, were upregulated in a dose- and time-dependent manner [19].
  • TLE-1 and BBC3/PUMA were identified as direct targets of SOX4 [20].

Analytical, diagnostic and therapeutic context of BBC3


  1. BBC3 mediates fenretinide-induced cell death in neuroblastoma. Wei, J.S., Whiteford, C.C., Cenacchi, N., Son, C.G., Khan, J. Oncogene (2005) [Pubmed]
  2. Degradation of the proapoptotic proteins Bik, Puma, and Bim with Bcl-2 domain 3 homology in Chlamydia trachomatis-infected cells. Dong, F., Pirbhai, M., Xiao, Y., Zhong, Y., Wu, Y., Zhong, G. Infect. Immun. (2005) [Pubmed]
  3. Chronic lymphocytic leukemia cells display p53-dependent drug-induced Puma upregulation. Mackus, W.J., Kater, A.P., Grummels, A., Evers, L.M., Hooijbrink, B., Kramer, M.H., Castro, J.E., Kipps, T.J., van Lier, R.A., van Oers, M.H., Eldering, E. Leukemia (2005) [Pubmed]
  4. Lamellar-to-hexagonalII phase transitions in the plasma membrane of isolated protoplasts after freeze-induced dehydration. Gordon-Kamm, W.J., Steponkus, P.L. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  5. Life in the balance: how BH3-only proteins induce apoptosis. Willis, S.N., Adams, J.M. Curr. Opin. Cell Biol. (2005) [Pubmed]
  6. The Noxa/Mcl-1 axis regulates susceptibility to apoptosis under glucose limitation in dividing T cells. Alves, N.L., Derks, I.A., Berk, E., Spijker, R., van Lier, R.A., Eldering, E. Immunity (2006) [Pubmed]
  7. 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]
  8. NF-kappaB and p53 are the dominant apoptosis-inducing transcription factors elicited by the HIV-1 envelope. Perfettini, J.L., Roumier, T., Castedo, M., Larochette, N., Boya, P., Raynal, B., Lazar, V., Ciccosanti, F., Nardacci, R., Penninger, J., Piacentini, M., Kroemer, G. J. Exp. Med. (2004) [Pubmed]
  9. Inhibition of staurosporine-induced activation of the proapoptotic multidomain Bcl-2 proteins Bax and Bak by three invasive chlamydial species. Zhong, Y., Weininger, M., Pirbhai, M., Dong, F., Zhong, G. J. Infect. (2006) [Pubmed]
  10. Suspected secondary thiafentanil intoxication in a captive mountain lion (Puma concolor). Wolfe, L.L., Miller, M.W. J. Wildl. Dis. (2005) [Pubmed]
  11. Puma(*)Mcl-1 interaction is not sufficient to prevent rapid degradation of Mcl-1. Mei, Y., Du, W., Yang, Y., Wu, M. Oncogene (2005) [Pubmed]
  12. Broad degradation of proapoptotic proteins with the conserved Bcl-2 homology domain 3 during infection with Chlamydia trachomatis. Ying, S., Seiffert, B.M., Häcker, G., Fischer, S.F. Infect. Immun. (2005) [Pubmed]
  13. Inhibition of glutathione synthesis overcomes Bcl-2-mediated topoisomerase inhibitor resistance and induces nonapoptotic cell death via mitochondrial-independent pathway. Yoshida, A., Takemura, H., Inoue, H., Miyashita, T., Ueda, T. Cancer Res. (2006) [Pubmed]
  14. Differential contribution of Puma and Noxa in dual regulation of p53-mediated apoptotic pathways. Shibue, T., Suzuki, S., Okamoto, H., Yoshida, H., Ohba, Y., Takaoka, A., Taniguchi, T. EMBO J. (2006) [Pubmed]
  15. Characterization of cell death pathways in human immunodeficiency virus-associated encephalitis. Nardacci, R., Antinori, A., Larocca, L.M., Arena, V., Amendola, A., Perfettini, J.L., Kroemer, G., Piacentini, M. Am. J. Pathol. (2005) [Pubmed]
  16. Regulation of p53 stability and function in HCT116 colon cancer cells. Kaeser, M.D., Pebernard, S., Iggo, R.D. J. Biol. Chem. (2004) [Pubmed]
  17. Low temperature protects mammalian cells from apoptosis initiated by various stimuli in vitro. Sakurai, T., Itoh, K., Liu, Y., Higashitsuji, H., Sumitomo, Y., Sakamaki, K., Fujita, J. Exp. Cell Res. (2005) [Pubmed]
  18. Activation of p53 signaling initiates apoptotic death in a cellular model of Parkinson's disease. Nair, V.D. Apoptosis (2006) [Pubmed]
  19. Mitochondria-mediated and p53-associated apoptosis induced in human cancer cells by a novel selenophene derivative, D-501036. Shiah, H.S., Lee, W.S., Juang, S.H., Hong, P.C., Lung, C.C., Chang, C.J., Chou, K.M., Chang, J.Y. Biochem. Pharmacol. (2007) [Pubmed]
  20. Sex-determining region Y box 4 is a transforming oncogene in human prostate cancer cells. Liu, P., Ramachandran, S., Ali Seyed, M., Scharer, C.D., Laycock, N., Dalton, W.B., Williams, H., Karanam, S., Datta, M.W., Jaye, D.L., Moreno, C.S. Cancer Res. (2006) [Pubmed]
  21. Changes in the net charge and subunit properties of ribulose bisphosphate carboxylase--oxygenase during cold hardening of Puma rye. Huner, N.P., Macdowall, F.D. Can. J. Biochem. (1979) [Pubmed]
  22. Changes in the heterogeneity of ribulosebisphosphate carboxylase-oxygenase in winter rye induced by cold hardening. Huner, N.P., Hayden, D.B. Can. J. Biochem. (1982) [Pubmed]
  23. Gastrointestinal helminths of free-ranging Florida panthers (Puma concolor coryi) and the efficacy of the current anthelmintic treatment protocol. Foster, G.W., Cunningham, M.W., Kinsella, J.M., McLaughlin, G., Forrester, D.J. J. Wildl. Dis. (2006) [Pubmed]
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