The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Bad  -  BCL2-associated agonist of cell death

Mus musculus

Synonyms: AI325008, BAD, Bbc2, Bbc6, Bcl-2-binding component 6, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Bad


High impact information on Bad

  • The susceptibility of a cell to a death signal is determined by these competing dimerizations in which levels of Bad influence the effectiveness of Bcl-2 versus Bcl-xL in repressing death [5].
  • When Bad dimerized with Bcl-xL, Bax was displaced and apoptosis was restored [5].
  • Both yeast two-hybrid screening and lambda expression cloning identified a novel interacting protein, Bad, whose homology to Bcl-2 is limited to the BH1 and BH2 domains [5].
  • In contrast, constitutively active forms of Bim and Bad failed to induce apoptosis in bax(-/-)bak(-/-) cells [6].
  • The BH3 only proteins, Bad and Bim, were also part of the death pathway repressed by IL-7 [7].

Chemical compound and disease context of Bad


Biological context of Bad

  • In addition, Bax but not Bim or Bad sensitized the bax(-/-)bak(-/-) cells to a wide variety of cell death stimuli including UV irradiation, chemotherapeutic agents, and ER stress [6].
  • Phosphorylation of Bad required Box1 but not Y449, suggesting that Jak1 also initiates an additional signaling cascade that accounts for approximately 10% of the survival function [11].
  • Whereas alphaNF markedly reduced the activation of B[a]P to reactive metabolites, as measured by covalent binding to macromolecules, it did not inhibit the up-regulation of phospho-Bad [12].
  • Concurrently, a down-regulation of the proapoptotic proteins FasL and Bad was detected in cortical lysates [13].
  • Growth factors promote cell survival through phosphorylation of Bad, resulting in its dissociation from Bcl-2 and Bcl-x(L) and its association with 14-3-3tau [14].

Anatomical context of Bad


Associations of Bad with chemical compounds

  • The BH3-only proteins Bim and Bad bind to the antiapoptotic Bcl-2 proteins and induce apoptosis in wild-type cells and cells from either bax(-/-) or bak(-/-) animals [6].
  • This neurotoxic effect was accompanied by up-regulation of the proapoptotic proteins FasL, Fas, and Bad and the active fragments of caspases-8 and -3 in cortical and hippocampal lysates [13].
  • ES cells exposed to 1 microM all-trans-retinoic acid on day 8, 9 and 10 of differentiation revealed increased expression of Bax and Bad compared to the vehicle-treated cells [19].
  • The levels of Bax and Bad proteins remained relatively constant during DMSO-induced differentiation [20].
  • There was also increased susceptibility to H2O2-induced apoptosis, decreased thymic expression of IL-7, decreased expression of an IL-7 downstream anti-apoptosis gene, Bcl-2, and increased expression of a pro-apoptotic gene, Bad [21].

Physical interactions of Bad

  • Bcl-xL and Bcl-w specifically interact with PP1alpha and Bad [22].
  • We utilize an interleukin-2 (IL-2)-dependent murine T-cell line to identify proteins that interact with Bad upon IL-2 stimulation or deprivation [23].

Enzymatic interactions of Bad

  • Pim-3 was also able to phosphorylate other sites in Bad in vitro, including Ser170, another potential in vivo site [24].
  • The data demonstrate that c-N-Ras may play a functional role in the regulation of steady-state phosphorylated Akt and serine 136-phosphorylated Bad (Ser(136)-pBad) [25].
  • Oxidative stress and the redox state are also implicated in the survival signaling pathway that involves phosphatidylinositol 3-kinase (PI3-K)/Akt and downstream signaling molecular bindings like Bad/Bcl-X(L) and phosphorylated Bad/14-3-3 [26].

Regulatory relationships of Bad


Other interactions of Bad

  • Thus, the inactivation of Bad contributes to the survival function of IL-7 [15].
  • Bak was barely detectable and Bad protein level decreased in cells undergoing apoptosis [32].
  • In contrast, a significant increase was observed in the anti-apoptotic member Bcl-2. mRNA expression of Bcl-w, Bad, and Bcl-x(L) was not significantly different between the control and TPN groups [33].
  • Interestingly, the levels of anti-apoptotic phospho-Bad (Ser155 and Ser112) had a biphasic increase after B[a]P or CPP treatment [12].
  • Finally, we showed that the inhibitory effect of LHRH on IGF-1-induced PKCalpha-mediated Akt activation was associated with a marked reduction in Bad phosphorylation and a substantial decrease in the ability of IGF-1 to rescue alphaT3 cells from apoptosis induced by serum starvation [34].

Analytical, diagnostic and therapeutic context of Bad


  1. Hypoxia-mediated down-regulation of Bid and Bax in tumors occurs via hypoxia-inducible factor 1-dependent and -independent mechanisms and contributes to drug resistance. Erler, J.T., Cawthorne, C.J., Williams, K.J., Koritzinsky, M., Wouters, B.G., Wilson, C., Miller, C., Demonacos, C., Stratford, I.J., Dive, C. Mol. Cell. Biol. (2004) [Pubmed]
  2. Adenovirus E1B 19-kDa death suppressor protein interacts with Bax but not with Bad. Chen, G., Branton, P.E., Yang, E., Korsmeyer, S.J., Shore, G.C. J. Biol. Chem. (1996) [Pubmed]
  3. Cycloheximide and actinomycin D delay death and affect bcl-2, bax, and Ice gene expression in astrocytes under in vitro ischemia. Yu, A.C., Yung, H.W., Hui, M.H., Lau, L.T., Chen, X.Q., Collins, R.A. J. Neurosci. Res. (2003) [Pubmed]
  4. Tacrolimus (FK506) attenuates biphasic cytochrome c release and Bad phosphorylation following transient cerebral ischemia in mice. Li, J.Y., Furuichi, Y., Matsuoka, N., Mutoh, S., Yanagihara, T. Neuroscience (2006) [Pubmed]
  5. Bad, a heterodimeric partner for Bcl-XL and Bcl-2, displaces Bax and promotes cell death. Yang, E., Zha, J., Jockel, J., Boise, L.H., Thompson, C.B., Korsmeyer, S.J. Cell (1995) [Pubmed]
  6. BH3-only proteins that bind pro-survival Bcl-2 family members fail to induce apoptosis in the absence of Bax and Bak. Zong, W.X., Lindsten, T., Ross, A.J., MacGregor, G.R., Thompson, C.B. Genes Dev. (2001) [Pubmed]
  7. Bax deficiency partially corrects interleukin-7 receptor alpha deficiency. Khaled, A.R., Li, W.Q., Huang, J., Fry, T.J., Khaled, A.S., Mackall, C.L., Muegge, K., Young, H.A., Durum, S.K. Immunity (2002) [Pubmed]
  8. Monogene and polygene therapy for the treatment of experimental prostate cancers by use of apoptotic genes bax and bad driven by the prostate-specific promoter ARR(2)PB. Zhang, Y., Yu, J., Unni, E., Shao, T.C., Nan, B., Snabboon, T., Kasper, S., Andriani, F., Denner, L., Marcelli, M. Hum. Gene Ther. (2002) [Pubmed]
  9. Overexpression of copper/zinc superoxide dismutase in transgenic mice protects against neuronal cell death after transient focal ischemia by blocking activation of the Bad cell death signaling pathway. Saito, A., Hayashi, T., Okuno, S., Ferrand-Drake, M., Chan, P.H. J. Neurosci. (2003) [Pubmed]
  10. Extracellular Bad fused to toxin transport domains induces apoptosis. Ichinose, M., Liu, X.H., Hagihara, N., Youle, R.J. Cancer Res. (2002) [Pubmed]
  11. Distinct regions of the interleukin-7 receptor regulate different Bcl2 family members. Jiang, Q., Li, W.Q., Hofmeister, R.R., Young, H.A., Hodge, D.R., Keller, J.R., Khaled, A.R., Durum, S.K. Mol. Cell. Biol. (2004) [Pubmed]
  12. Polycyclic aromatic hydrocarbons induce both apoptotic and anti-apoptotic signals in Hepa1c1c7 cells. Solhaug, A., Refsnes, M., Låg, M., Schwarze, P.E., Husøy, T., Holme, J.A. Carcinogenesis (2004) [Pubmed]
  13. Modulation of apoptosis in the mouse brain after morphine treatments and morphine withdrawal. Emeterio, E.P., Tramullas, M., Hurlé, M.A. J. Neurosci. Res. (2006) [Pubmed]
  14. p21-activated kinase 1 phosphorylates the death agonist bad and protects cells from apoptosis. Schürmann, A., Mooney, A.F., Sanders, L.C., Sells, M.A., Wang, H.G., Reed, J.C., Bokoch, G.M. Mol. Cell. Biol. (2000) [Pubmed]
  15. Interleukin-7 inactivates the pro-apoptotic protein Bad promoting T cell survival. Li, W.Q., Jiang, Q., Khaled, A.R., Keller, J.R., Durum, S.K. J. Biol. Chem. (2004) [Pubmed]
  16. Developmental regulation of Bcl-2 family protein expression in the involuting mammary gland. Metcalfe, A.D., Gilmore, A., Klinowska, T., Oliver, J., Valentijn, A.J., Brown, R., Ross, A., MacGregor, G., Hickman, J.A., Streuli, C.H. J. Cell. Sci. (1999) [Pubmed]
  17. High glucose promotes mesangial cell apoptosis by oxidant-dependent mechanism. Kang, B.P., Frencher, S., Reddy, V., Kessler, A., Malhotra, A., Meggs, L.G. Am. J. Physiol. Renal Physiol. (2003) [Pubmed]
  18. Akt protects mouse hepatocytes from TNF-alpha- and Fas-mediated apoptosis through NK-kappa B activation. Hatano, E., Brenner, D.A. Am. J. Physiol. Gastrointest. Liver Physiol. (2001) [Pubmed]
  19. Expression of selected apoptosis related genes, MIF, IGIF and TNF alpha, during retinoic acid-induced neural differentiation in murine embryonic stem cells. Sarkar, S.A., Sharma, R.P. Cell Struct. Funct. (2002) [Pubmed]
  20. Bcl-XL induction during terminal differentiation of friend erythroleukaemia cells correlates with delay of apoptosis and loss of proliferative capacity but not with haemoglobinization. Hafid-Medheb, K., Poindessous-Jazat, V., Augery-Bourget, Y., Hanania, N., Robert-Lézénès, J. Cell Death Differ. (1999) [Pubmed]
  21. Phenotype of genetically regulated thymic involution in young BXD RI strains of mice. Wang, X., Hsu, H.C., Wang, Y., Edwards, C.K., Yang, P., Wu, Q., Mountz, J.D. Scand. J. Immunol. (2006) [Pubmed]
  22. The anti-apoptotic molecules Bcl-xL and Bcl-w target protein phosphatase 1alpha to Bad. Ayllón, V., Cayla, X., García, A., Fleischer, A., Rebollo, A. Eur. J. Immunol. (2002) [Pubmed]
  23. Protein phosphatase 1alpha is a Ras-activated Bad phosphatase that regulates interleukin-2 deprivation-induced apoptosis. Ayllón, V., Martínez-A, C., García, A., Cayla, X., Rebollo, A. EMBO J. (2000) [Pubmed]
  24. Pim kinases phosphorylate multiple sites on Bad and promote 14-3-3 binding and dissociation from Bcl-XL. Macdonald, A., Campbell, D.G., Toth, R., McLauchlan, H., Hastie, C.J., Arthur, J.S. BMC Cell Biol. (2006) [Pubmed]
  25. Endogenous c-N-Ras provides a steady-state anti-apoptotic signal. Wolfman, J.C., Wolfman, A. J. Biol. Chem. (2000) [Pubmed]
  26. Mitochondrial dysfunction and oxidative stress as determinants of cell death/survival in stroke. Chan, P.H. Ann. N. Y. Acad. Sci. (2005) [Pubmed]
  27. Bad is a BH3 domain-containing protein that forms an inactivating dimer with Bcl-XL. Kelekar, A., Chang, B.S., Harlan, J.E., Fesik, S.W., Thompson, C.B. Mol. Cell. Biol. (1997) [Pubmed]
  28. PTEN modulates cell cycle progression and cell survival by regulating phosphatidylinositol 3,4,5,-trisphosphate and Akt/protein kinase B signaling pathway. Sun, H., Lesche, R., Li, D.M., Liliental, J., Zhang, H., Gao, J., Gavrilova, N., Mueller, B., Liu, X., Wu, H. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  29. Genetic inhibition or activation of JNK1/2 protects the myocardium from ischemia-reperfusion-induced cell death in vivo. Kaiser, R.A., Liang, Q., Bueno, O., Huang, Y., Lackey, T., Klevitsky, R., Hewett, T.E., Molkentin, J.D. J. Biol. Chem. (2005) [Pubmed]
  30. bFGF inhibits the activation of caspase-3 and apoptosis of P19 embryonal carcinoma cells during neuronal differentiation. Miho, Y., Kouroku, Y., Fujita, E., Mukasa, T., Urase, K., Kasahara, T., Isoai, A., Momoi, M.Y., Momoi, T. Cell Death Differ. (1999) [Pubmed]
  31. Transforming growth factor-beta 1 increases bad phosphorylation and protects neurons against damage. Zhu, Y., Yang, G.Y., Ahlemeyer, B., Pang, L., Che, X.M., Culmsee, C., Klumpp, S., Krieglstein, J. J. Neurosci. (2002) [Pubmed]
  32. v-Abl protein tyrosine kinase (PTK) mediated suppression of apoptosis is associated with the up-regulation of Bcl-XL. Chen, Q., Turner, J., Watson, A.J., Dive, C. Oncogene (1997) [Pubmed]
  33. Total parenteral nutrition-induced apoptosis in mouse intestinal epithelium: regulation by the Bcl-2 protein family. Wildhaber, B.E., Lynn, K.N., Yang, H., Teitelbaum, D.H. Pediatr. Surg. Int. (2002) [Pubmed]
  34. The luteinizing hormone-releasing hormone inhibits the anti-apoptotic activity of insulin-like growth factor-1 in pituitary alphaT3 cells by protein kinase Calpha-mediated negative regulation of Akt. Rose, A., Froment, P., Perrot, V., Quon, M.J., LeRoith, D., Dupont, J. J. Biol. Chem. (2004) [Pubmed]
  35. Histone deacetylase inhibitor, FK228, induces apoptosis and suppresses cell proliferation of human glioblastoma cells in vitro and in vivo. Sawa, H., Murakami, H., Kumagai, M., Nakasato, M., Yamauchi, S., Matsuyama, N., Tamura, Y., Satone, A., Ide, W., Hashimoto, I., Kamada, H. Acta Neuropathol. (2004) [Pubmed]
  36. Bad-dependent rafts alteration is a consequence of an early intracellular signal triggered by interleukin-4 deprivation. Fleischer, A., Ghadiri, A., Dessauge, F., Duhamel, M., Cayla, X., Garcia, A., Rebollo, A. Mol. Cancer Res. (2004) [Pubmed]
  37. Identification of a novel phosphorylation site, Ser-170, as a regulator of bad pro-apoptotic activity. Dramsi, S., Scheid, M.P., Maiti, A., Hojabrpour, P., Chen, X., Schubert, K., Goodlett, D.R., Aebersold, R., Duronio, V. J. Biol. Chem. (2002) [Pubmed]
  38. Simvastatin induces activation of the serine-threonine protein kinase AKT and increases survival of isolated human pancreatic islets. Contreras, J.L., Smyth, C.A., Bilbao, G., Young, C.J., Thompson, J.A., Eckhoff, D.E. Transplantation (2002) [Pubmed]
WikiGenes - Universities