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Gene Review

Bad  -  BCL2-associated agonist of cell death

Rattus norvegicus

Synonyms: BAD, Bcl-2-binding component 6, Bcl-xL/Bcl-2-associated death promoter, Bcl2 antagonist of cell death, Bcl2-associated agonist of cell death
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Disease relevance of Bad


High impact information on Bad

  • Down-regulation of PI(3)K by ceramide results in inhibition of the kinase Akt and decreased phosphorylation of the death effector Bad [6].
  • Western blot analysis revealed that the content of Bcl-X(L) (but not of Bcl-2, BAX, Bad, and Bim) significantly decreased in thymocytes after CLP [7].
  • In in vitro systems, this constitutively active cleaved form of CaN has been reported to lead to apoptosis via dephosphorylation of the proapoptotic Bcl-2 family member, Bad [8].
  • Taken together, our results show that Akt promotes cell survival by intervening in the apoptosis cascade before cytochrome c release and caspase activation via a mechanism that is distinct from Bad phosphorylation [9].
  • To define the distal element of the antiapoptotic cascade, we tested the hypothesis that IGF-I inhibits the influence of the proapoptotic gene Bad [10].

Biological context of Bad

  • We have previously shown that sublytic C5b-9 complexes, through posttranslational regulation of Bad, inhibit the mitochondrial pathway of apoptosis induced by serum deprivation [11].
  • This study investigated whether it is Bad phosphorylation or NF-kappa B activation that provides the anti-apoptotic effects of Akt, and the data suggested that NF-kappa B is probably the principal contributor to the downstream activation of the PI3-kinase-Akt pathway [12].
  • We conclude that oxidative stress may play a role in modulating Akt/Bad signaling and subsequent motor neuron survival after SCI [1].
  • Dimerization of Bad with 14-3-3 in the cytosol was increased whereas Bad/Bcl-XL binding in the mitochondria was decreased after SCI [1].
  • The phosphoinositide-3-kinase (PI3K)/protein kinase B (PKB)/Bad signal transduction pathway is engaged in the control of apoptosis in many different cell types, particularly through phosphorylation of the Bcl-2 family protein Bad [13].

Anatomical context of Bad


Associations of Bad with chemical compounds

  • Treatment of retinal tissue cultures with forskolin, which increases intracellular levels of cAMP, partially blocked apoptosis induced by both anisomycin and 2-aminopurine, but not by LY294002, whereas forskolin invariably induced phosphorylation of Bad on both Ser112 and Ser136 [13].
  • CONCLUSIONS: Ethanol-induced alterations of Bad-related mechanisms at P4 favor a prodeath response [15].
  • This study investigated whether estradiol modulates the anti-apoptotic signal through the activation of Akt and its downstream targets, including Bad, Bcl-x(L), and 14-3-3 [3].
  • Similarly, a peptide derived from the BH3 domain of Bad stimulates Bax activity only in the presence of Bcl-xL [16].
  • Phosphatidylinositol 3-phosphate kinase activity was also responsible for the phosphorylation of Bad at Ser112 and Ser136 [17].

Enzymatic interactions of Bad

  • Furthermore, while anti-apoptotic markers, Bcl-2 and phosphorylated Bad, were down-regulated, pro-apoptotic markers, active caspase-3 and Bax, were up-regulated, resulting in the appearance of apoptotic cells in the penile tIssues of OLETF rats [18].
  • Whereas an upregulation of Bcl-xL and a downregulation of Bax seemed to contribute to decreased apoptosis in burn rat neutrophils at 2 h of incubation, the decreased apoptosis at 8 h appeared to be associated with a decrease in Bax and increased phosphorylated Bad [19].

Regulatory relationships of Bad

  • Oxidative stress-induced early apoptosis was linked to its ability to inhibit not only the expression of Bcl-2 and Bcl-XL but the production of antioxidant enzymes as well and to stimulate Bad expression [20].

Other interactions of Bad

  • Coimmunoprecipitation analysis demonstrated that although Bcl-2-associated death promoter (Bad) constitutively bound 14-3-3, there was no interaction between Bid and 14-3-3 in control brain [21].
  • The present study investigated EtOH effects on mechanisms related to activities of Bad, a proapoptotic member of the Bcl-2 gene family, to further characterize processes underlying these disparate EtOH sensitivities [15].
  • Concomitantly, these treatments led to a 2.5-, 4.0- and 4.0-fold increase in Bad while a slight decrease in Bax was observed [22].
  • Caspase-dependent cleavage of Bad to a 15-kDa fragment increases its proapoptogenic capacity [15].
  • PKB is constitutively phosphorylated in retinal tissue in vitro, whereas Bad was dephosphorylated both in Ser112 and Ser136 [13].

Analytical, diagnostic and therapeutic context of Bad

  • Both splice variants of Bad interacted with the antiapoptotic molecule Bcl-w as shown by yeast two-hybrid assay and by co-immunoprecipitation experiments from transfected cells. mRNA expression for the two variants of bad were detected in all neonatal and adult rat tissues tested [14].
  • Using Western blot analysis, we found that levels of phosphorylated Bad, but not total Bad protein, decreased under exposure to WIN 55,212-2 [2].
  • These findings suggest that modulation of MAP kinase and Akt expression, Bcl-xL, Bcl-xs, Bcl-2 and Bad proteins by finasteride may be, in part, responsible for the anti-proliferative and apoptotic effect of this drug seen clinically and in animal models [22].
  • Doses greater than 1.5 g/kg produced significant decreases in Bcl(2) and significant increases in Bad and Bax mRNA during the 8-h period after treatment [23].
  • Semi-quantitative reverse transcriptase with polymerase chain reaction (PCR) techniques were used to determine the expression levels of pro-apoptotic factors Bad and Bax, and anti-apoptotic Bcl(2) mRNA [23].


  1. Akt/Bad signaling and motor neuron survival after spinal cord injury. Yu, F., Sugawara, T., Maier, C.M., Hsieh, L.B., Chan, P.H. Neurobiol. Dis. (2005) [Pubmed]
  2. Cannabinoids down-regulate PI3K/Akt and Erk signalling pathways and activate proapoptotic function of Bad protein. Ellert-Miklaszewska, A., Kaminska, B., Konarska, L. Cell. Signal. (2005) [Pubmed]
  3. Estradiol prevents the injury-induced decrease of Akt activation and Bad phosphorylation. Won, C.K., Ha, S.J., Noh, H.S., Kang, S.S., Cho, G.J., Choi, W.S., Koh, P.O. Neurosci. Lett. (2005) [Pubmed]
  4. Cardioprotective effect of chronic hyperglycemia: effect on hypoxia-induced apoptosis and necrosis. Schaffer, S.W., Croft, C.B., Solodushko, V. Am. J. Physiol. Heart Circ. Physiol. (2000) [Pubmed]
  5. Altered Bad localization and interaction between Bad and Bcl-xL in the hippocampus after transient global ischemia. Abe, T., Takagi, N., Nakano, M., Furuya, M., Takeo, S. Brain Res. (2004) [Pubmed]
  6. Inhibition of the anti-apoptotic PI(3)K/Akt/Bad pathway by stress. Zundel, W., Giaccia, A. Genes Dev. (1998) [Pubmed]
  7. Protective effects of anti-C5a in sepsis-induced thymocyte apoptosis. Guo, R.F., Huber-Lang, M., Wang, X., Sarma, V., Padgaonkar, V.A., Craig, R.A., Riedemann, N.C., McClintock, S.D., Hlaing, T., Shi, M.M., Ward, P.A. J. Clin. Invest. (2000) [Pubmed]
  8. Calcineurin cleavage is triggered by elevated intraocular pressure, and calcineurin inhibition blocks retinal ganglion cell death in experimental glaucoma. Huang, W., Fileta, J.B., Dobberfuhl, A., Filippopolous, T., Guo, Y., Kwon, G., Grosskreutz, C.L. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  9. Akt/Protein kinase B inhibits cell death by preventing the release of cytochrome c from mitochondria. Kennedy, S.G., Kandel, E.S., Cross, T.K., Hay, N. Mol. Cell. Biol. (1999) [Pubmed]
  10. Regulation of vascular smooth muscle cell apoptosis. Modulation of bad by a phosphatidylinositol 3-kinase-dependent pathway. Bai, H., Pollman, M.J., Inishi, Y., Gibbons, G.H. Circ. Res. (1999) [Pubmed]
  11. C5b-9 terminal complex protects oligodendrocytes from apoptotic cell death by inhibiting caspase-8 processing and up-regulating FLIP. Cudrici, C., Niculescu, F., Jensen, T., Zafranskaia, E., Fosbrink, M., Rus, V., Shin, M.L., Rus, H. J. Immunol. (2006) [Pubmed]
  12. The PI3-kinase-Akt pathway promotes mesangial cell survival and inhibits apoptosis in vitro via NF-kappa B and Bad. Shimamura, H., Terada, Y., Okado, T., Tanaka, H., Inoshita, S., Sasaki, S. J. Am. Soc. Nephrol. (2003) [Pubmed]
  13. Selective involvement of the PI3K/PKB/bad pathway in retinal cell death. Campos, C.B., Bédard, P.A., Linden, R. J. Neurobiol. (2003) [Pubmed]
  14. Functional characterization of two splice variants of rat bad and their interaction with Bcl-w in sympathetic neurons. Hamnér, S., Arumäe, U., Li-Ying, Y., Sun, Y.F., Saarma, M., Lindholm, D. Mol. Cell. Neurosci. (2001) [Pubmed]
  15. Effects of acute ethanol exposure on regulatory mechanisms of Bcl-2-associated apoptosis promoter, bad, in neonatal rat cerebellum: differential effects during vulnerable and resistant developmental periods. Siler-Marsiglio, K.I., Madorsky, I., Pan, Q., Paiva, M., Neeley, A.W., Shaw, G., Heaton, M.B. Alcohol. Clin. Exp. Res. (2006) [Pubmed]
  16. Minimal BH3 peptides promote cell death by antagonizing anti-apoptotic proteins. Moreau, C., Cartron, P.F., Hunt, A., Meflah, K., Green, D.R., Evan, G., Vallette, F.M., Juin, P. J. Biol. Chem. (2003) [Pubmed]
  17. C5b-9 terminal complement complex protects oligodendrocytes from death by regulating Bad through phosphatidylinositol 3-kinase/Akt pathway. Soane, L., Cho, H.J., Niculescu, F., Rus, H., Shin, M.L. J. Immunol. (2001) [Pubmed]
  18. Diminished penile expression of vascular endothelial growth factor and its receptors at the insulin-resistant stage of a type II diabetic rat model: a possible cause for erectile dysfunction in diabetes. Jesmin, S., Sakuma, I., Salah-Eldin, A., Nonomura, K., Hattori, Y., Kitabatake, A. J. Mol. Endocrinol. (2003) [Pubmed]
  19. Suppression of mitochondria-dependent neutrophil apoptosis with thermal injury. Hu, Z., Sayeed, M.M. Am. J. Physiol., Cell Physiol. (2004) [Pubmed]
  20. Idoxifene and estradiol enhance antiapoptotic activity through estrogen receptor-beta in cultured rat hepatocytes. Inoue, H., Shimizu, I., Lu, G., Itonaga, M., Cui, X., Okamura, Y., Shono, M., Honda, H., Inoue, S., Muramatsu, M., Ito, S. Dig. Dis. Sci. (2003) [Pubmed]
  21. Interaction of 14-3-3 with Bid during seizure-induced neuronal death. Shinoda, S., Schindler, C.K., Quan-Lan, J., Saugstad, J.A., Taki, W., Simon, R.P., Henshall, D.C. J. Neurochem. (2003) [Pubmed]
  22. Induction of apoptosis in rat ventral prostate by finasteride is associated with alteration in MAP kinase pathways and Bcl-2 related family of proteins. Huynh, H. Int. J. Oncol. (2002) [Pubmed]
  23. Altered expression of Bcl2, Bad and Bax mRNA occurs in the rat cerebellum within hours after ethanol exposure on postnatal day 4 but not on postnatal day 9. Ge, Y., Belcher, S.M., Pierce, D.R., Light, K.E. Brain Res. Mol. Brain Res. (2004) [Pubmed]
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