Bad

Summary

Gene Symbol: Bad
Description: BCL2-associated agonist of cell death
Alias: AI325008, Bbc2, bcl2-associated agonist of cell death, bcl-2-binding component 6, bcl-xL/Bcl-2-associated death promoter, bcl2 antagonist of cell death
Species: mouse
Products:     Bad

Top Publications

  1. Ulett G, Maclean K, Nekkalapu S, Cleveland J, Adderson E. Mechanisms of group B streptococcal-induced apoptosis of murine macrophages. J Immunol. 2005;175:2555-62 pubmed
    ..in murine macrophages GBS induces unique changes in the regulation and localization of the apoptotic regulators Bad, 14-3-3, and Omi/high-temperature requirement A2 and leads to the release of cytochrome c and the activation of ..
  2. Masters S, Yang H, Datta S, Greenberg M, Fu H. 14-3-3 inhibits Bad-induced cell death through interaction with serine-136. Mol Pharmacol. 2001;60:1325-31 pubmed
    ..One target of 14-3-3 is the proapoptotic Bcl-2 family member Bad. Serine phosphorylation of Bad is associated with 14-3-3 binding and inhibition of Bad-induced cell death, but the ..
  3. Chiang C, Kanies C, Kim K, Fang W, Parkhurst C, Xie M, et al. Protein phosphatase 2A dephosphorylation of phosphoserine 112 plays the gatekeeper role for BAD-mediated apoptosis. Mol Cell Biol. 2003;23:6350-62 pubmed
    b>BAD, a proapoptotic molecule of the BCL2 family, is regulated by reversible phosphorylation...
  4. Wang S, Denny T, Steinbrecher U, Duronio V. Phosphorylation of Bad is not essential for PKB-mediated survival signaling in hemopoietic cells. Apoptosis. 2005;10:341-8 pubmed
    This study was designed to investigate Bad phosphorylation at several of its key regulatory Ser residues in cytokine-dependent hemopoietic cells...
  5. Dramsi S, Scheid M, Maiti A, Hojabrpour P, Chen X, Schubert K, et al. Identification of a novel phosphorylation site, Ser-170, as a regulator of bad pro-apoptotic activity. J Biol Chem. 2002;277:6399-405 pubmed
    b>Bad is a pro-apoptotic member of the Bcl-2 family of proteins that is thought to exert a death-promoting effect by heterodimerization with Bcl-X(L), nullifying its anti-apoptotic activity...
  6. del Peso L, Gonzalez Garcia M, Page C, Herrera R, Nunez G. Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt. Science. 1997;278:687-9 pubmed
    b>BAD is a distant member of the Bcl-2 family that promotes cell death. Phosphorylation of BAD prevents this...
  7. Datta S, Ranger A, Lin M, Sturgill J, Ma Y, Cowan C, et al. Survival factor-mediated BAD phosphorylation raises the mitochondrial threshold for apoptosis. Dev Cell. 2002;3:631-43 pubmed
    ..with the phosphorylation and inactivation of multiple proapoptotic proteins, including the BCL-2 family member BAD. However, the physiological events required for growth factors to block cell death are not well characterized...
  8. Opferman J, Letai A, Beard C, Sorcinelli M, Ong C, Korsmeyer S. Development and maintenance of B and T lymphocytes requires antiapoptotic MCL-1. Nature. 2003;426:671-6 pubmed
    ..Thus, MCL-1, which selectively inhibits the proapoptotic protein BIM, is essential both early in lymphoid development and later on in the maintenance of mature lymphocytes. ..
  9. Frenzel A, Labi V, Chmelewskij W, Ploner C, Geley S, Fiegl H, et al. Suppression of B-cell lymphomagenesis by the BH3-only proteins Bmf and Bad. Blood. 2010;115:995-1005 pubmed publisher
    ..the BH3-only proapoptotic Bcl-2 family members Bcl-2 modifying factor (Bmf) and Bcl-2 antagonist of cell death (Bad) are potent antagonists of c-Myc-driven B-cell lymphomagenesis...

More Information

Publications83

  1. Gilmore A, Valentijn A, Wang P, Ranger A, Bundred N, O Hare M, et al. Activation of BAD by therapeutic inhibition of epidermal growth factor receptor and transactivation by insulin-like growth factor receptor. J Biol Chem. 2002;277:27643-50 pubmed
    ..We showed that it prevents cell survival by activating the pro-apoptotic protein BAD. Moreover, we demonstrate that IGF transactivates the EGF receptor and that ZD1839 blocks IGF-mediated ..
  2. Kelly P, White M, Goschnick M, Fairfax K, Tarlinton D, Kinkel S, et al. Individual and overlapping roles of BH3-only proteins Bim and Bad in apoptosis of lymphocytes and platelets and in suppression of thymic lymphoma development. Cell Death Differ. 2010;17:1655-64 pubmed publisher
    BH3-only proteins, such as Bim and Bad, contribute to tissue homeostasis by initiating apoptosis in a cell type- and stimulus-specific manner...
  3. Jiao S, Li Z. Nonapoptotic function of BAD and BAX in long-term depression of synaptic transmission. Neuron. 2011;70:758-72 pubmed publisher
    ..Here we show that caspase-3 is activated by the BAD-BAX cascade for LTD induction...
  4. Yan J, Xiang J, Lin Y, Ma J, Zhang J, Zhang H, et al. Inactivation of BAD by IKK inhibits TNF?-induced apoptosis independently of NF-?B activation. Cell. 2013;152:304-15 pubmed publisher
    ..Here, we report that inactivation of the BH3-only protein BAD by IKK independently of NF-?B activation suppresses TNF?-induced apoptosis...
  5. Ekert P, Jabbour A, Manoharan A, Heraud J, Yu J, Pakusch M, et al. Cell death provoked by loss of interleukin-3 signaling is independent of Bad, Bim, and PI3 kinase, but depends in part on Puma. Blood. 2006;108:1461-8 pubmed
    ..b>Bad and Bim are 2 such BH3-only Bcl-2 family members that have been implicated as key initiators in apoptosis following ..
  6. Ranger A, Zha J, Harada H, Datta S, Danial N, Gilmore A, et al. Bad-deficient mice develop diffuse large B cell lymphoma. Proc Natl Acad Sci U S A. 2003;100:9324-9 pubmed
    The proapoptotic activity of the "BH3-only" molecule BAD can be differentially regulated by survival factor signaling...
  7. Chen L, Willis S, Wei A, Smith B, Fletcher J, Hinds M, et al. Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function. Mol Cell. 2005;17:393-403 pubmed
    ..Bim and Puma potently engaged all the prosurvival proteins comparably. Bad, however, bound tightly to Bcl-2, Bcl-xL, and Bcl-w but only weakly to A1 and not to Mcl-1...
  8. Danial N, Gramm C, Scorrano L, Zhang C, Krauss S, Ranger A, et al. BAD and glucokinase reside in a mitochondrial complex that integrates glycolysis and apoptosis. Nature. 2003;424:952-6 pubmed
    ..The activity of BAD, a pro-apoptotic BCL-2 family member, is regulated by phosphorylation in response to growth/survival factors...
  9. Willis S, Fletcher J, Kaufmann T, van Delft M, Chen L, Czabotar P, et al. Apoptosis initiated when BH3 ligands engage multiple Bcl-2 homologs, not Bax or Bak. Science. 2007;315:856-9 pubmed
    ..Our results indicate that BH3-only proteins induce apoptosis at least primarily by engaging the multiple pro-survival relatives guarding Bax and Bak. ..
  10. Fischer S, Bouillet P, O Donnell K, Light A, Tarlinton D, Strasser A. Proapoptotic BH3-only protein Bim is essential for developmentally programmed death of germinal center-derived memory B cells and antibody-forming cells. Blood. 2007;110:3978-84 pubmed
    ..We have identified for the first time the physiologic mechanisms for killing low-affinity antibody-expressing B cells in an immune response and have shown this to be dependent on the BH3-only protein Bim. ..
  11. Zha J, Harada H, Yang E, Jockel J, Korsmeyer S. Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14-3-3 not BCL-X(L). Cell. 1996;87:619-28 pubmed
    ..One distant member, BAD, heterodimerizes with BCL-X(L) or BCL-2, neutralizing their protective effect and promoting cell death...
  12. Jeong S, Gaume B, Lee Y, Hsu Y, Ryu S, Yoon S, et al. Bcl-x(L) sequesters its C-terminal membrane anchor in soluble, cytosolic homodimers. EMBO J. 2004;23:2146-55 pubmed
    ..b>Bad binding to Bcl-x(L) dissociates the homodimers and triggers Bcl-x(L) binding to mitochondrial membranes...
  13. Datta S, Katsov A, Hu L, Petros A, Fesik S, Yaffe M, et al. 14-3-3 proteins and survival kinases cooperate to inactivate BAD by BH3 domain phosphorylation. Mol Cell. 2000;6:41-51 pubmed
    ..We report that survival factors trigger the phosphorylation of the proapoptotic Bcl-2 family member BAD at a site (Ser-155) within the BAD BH3 domain...
  14. Yan B, Zemskova M, Holder S, Chin V, Kraft A, Koskinen P, et al. The PIM-2 kinase phosphorylates BAD on serine 112 and reverses BAD-induced cell death. J Biol Chem. 2003;278:45358-67 pubmed
    ..However, the kinase can phosphorylate the pro-apoptotic protein BAD on serine 112, which accounts in part for its ability to reverse Bad-induced cell death...
  15. Danial N, Walensky L, Zhang C, Choi C, Fisher J, Molina A, et al. Dual role of proapoptotic BAD in insulin secretion and beta cell survival. Nat Med. 2008;14:144-53 pubmed publisher
    The proapoptotic BCL-2 family member BAD resides in a glucokinase-containing complex that regulates glucose-driven mitochondrial respiration...
  16. Blume Jensen P, Janknecht R, Hunter T. The kit receptor promotes cell survival via activation of PI 3-kinase and subsequent Akt-mediated phosphorylation of Bad on Ser136. Curr Biol. 1998;8:779-82 pubmed
    ..of the serine/threonine, we found that, in response to SCF Akt became activated and mediated phosphorylation of Bad, a pro-apoptotic molecule, in a PI-3-kinase-dependent manner...
  17. Ibata Ombetta S, Idziorek T, Trinel P, Poulain D, Jouault T. Candida albicans phospholipomannan promotes survival of phagocytosed yeasts through modulation of bad phosphorylation and macrophage apoptosis. J Biol Chem. 2003;278:13086-93 pubmed
    ..by J774 and disregulation of the ERK1/2 signal transduction pathway was associated downstream with a reduction in Bad Ser-112 phosphorylation and disappearance of free Bcl-2...
  18. Benetti L, Munger J, Roizman B. The herpes simplex virus 1 US3 protein kinase blocks caspase-dependent double cleavage and activation of the proapoptotic protein BAD. J Virol. 2003;77:6567-73 pubmed
    ..Further studies revealed that the kinase also blocks programmed cell death induced by the proapoptotic protein BAD. Here we report the effects of the U(S)3 protein kinase on the function and state of a murine BAD protein...
  19. Wikstrom J, Katzman S, Mohamed H, Twig G, Graf S, Heart E, et al. beta-Cell mitochondria exhibit membrane potential heterogeneity that can be altered by stimulatory or toxic fuel levels. Diabetes. 2007;56:2569-78 pubmed
    ..We identified BAD, a proapoptotic BCL-2 family member previously implicated in mitochondrial recruitment of glucokinase, as a ..
  20. Zhang Y, Yu J, Unni E, Shao T, Nan B, Snabboon T, et al. 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. Hum Gene Ther. 2002;13:2051-64 pubmed
    ..In this investigation we present data generated with adenovirus AvARR(2)PB-Bad, in which the apoptotic gene bad was placed under the control of the dihydrotestosterone (DHT)-inducible third-..
  21. Han J, Flemington C, Houghton A, Gu Z, Zambetti G, Lutz R, et al. Expression of bbc3, a pro-apoptotic BH3-only gene, is regulated by diverse cell death and survival signals. Proc Natl Acad Sci U S A. 2001;98:11318-23 pubmed
    ..These results suggest that the transcriptional regulation of bbc3 contributes to the transduction of diverse cell death and survival signals. ..
  22. Ayllon V, Fleischer A, Cayla X, Garcia A, Rebollo A. Segregation of Bad from lipid rafts is implicated in the induction of apoptosis. J Immunol. 2002;168:3387-93 pubmed
    ..Using coimmunoprecipitation experiments we demonstrate that Bad is not associated to 14-3-3 protein, suggesting a new mechanism for the control of the proapoptotic role of Bad...
  23. Cabon L, Galán Malo P, Bouharrour A, Delavallée L, Brunelle Navas M, Lorenzo H, et al. BID regulates AIF-mediated caspase-independent necroptosis by promoting BAX activation. Cell Death Differ. 2012;19:245-56 pubmed publisher
    ..Altogether, our data reveal that, as in caspase-dependent apoptosis, BH3-only proteins are key regulators of caspase-independent necroptosis. ..
  24. Hashimoto A, Hirose K, Iino M. BAD detects coincidence of G2/M phase and growth factor deprivation to regulate apoptosis. J Biol Chem. 2005;280:26225-32 pubmed
    b>BAD, a member of the Bcl-2 protein family, promotes mitochondria-dependent apoptosis. Here, we report that BAD dissociates from 14-3-3zeta at each G2/M phase of proliferating lymphoid cells...
  25. Kuper C, Bartels H, Beck F, Neuhofer W. Cyclooxygenase-2-dependent phosphorylation of the pro-apoptotic protein Bad inhibits tonicity-induced apoptosis in renal medullary cells. Kidney Int. 2011;80:938-945 pubmed publisher
    ..E2 (PGE2) promotes cell survival by phosphorylation and, hence, inactivation of the pro-apoptotic protein Bad during hypertonic stress in Madin-Darby canine kidney (MDCK) cells in vitro...
  26. Naik E, Michalak E, Villunger A, Adams J, Strasser A. Ultraviolet radiation triggers apoptosis of fibroblasts and skin keratinocytes mainly via the BH3-only protein Noxa. J Cell Biol. 2007;176:415-24 pubmed
    ..Collectively, these results demonstrate that UVR activates the Bcl-2-regulated apoptotic pathway predominantly through activation of Noxa and, depending on cellular context, Puma. ..
  27. Donovan N, Becker E, Konishi Y, Bonni A. JNK phosphorylation and activation of BAD couples the stress-activated signaling pathway to the cell death machinery. J Biol Chem. 2002;277:40944-9 pubmed
    ..We have found that JNK catalyzes the phosphorylation of the BH3-only protein BAD at the distinct site of serine 128 in vitro...
  28. Neithardt A, Farshori M, Shah F, Catt K, Shah B. Dependence of GnRH-induced phosphorylation of CREB and BAD on EGF receptor transactivation in GT1-7 neuronal cells. J Cell Physiol. 2006;208:586-93 pubmed
    ..growth factor (EGF) caused rapid phosphorylation of cyclic AMP response element binding protein (CREB) and BAD. The selective epidermal growth factor receptor (EGF-R) antagonist, AG1478, attenuates the phosphorylation of these ..
  29. Santidrian A, González Gironès D, Iglesias Serret D, Coll Mulet L, Cosialls A, de Frias M, et al. AICAR induces apoptosis independently of AMPK and p53 through up-regulation of the BH3-only proteins BIM and NOXA in chronic lymphocytic leukemia cells. Blood. 2010;116:3023-32 pubmed publisher
    ..These findings support the notion that AICAR is an interesting alternative therapeutic option for CLL patients with impaired p53 function and resistance to conventional chemotherapy. ..
  30. Du Y, Lewis B, Hanahan D, Varmus H. Assessing tumor progression factors by somatic gene transfer into a mouse model: Bcl-xL promotes islet tumor cell invasion. PLoS Biol. 2007;5:e276 pubmed
    ..In addition, myosin Va was identified as a novel Bcl-xL-interacting protein that might mediate the effects of Bcl-xL on tumor cell migration and invasion. ..
  31. Schurmann A, Mooney A, Sanders L, Sells M, Wang H, Reed J, et al. p21-activated kinase 1 phosphorylates the death agonist bad and protects cells from apoptosis. Mol Cell Biol. 2000;20:453-61 pubmed
    b>Bad is a critical regulatory component of the intrinsic cell death machinery that exerts its death-promoting effect upon heterodimerization with the antiapoptotic proteins Bcl-2 and Bcl-x(L)...
  32. Di Poï N, Ng C, Tan N, Yang Z, Hemmings B, Desvergne B, et al. Epithelium-mesenchyme interactions control the activity of peroxisome proliferator-activated receptor beta/delta during hair follicle development. Mol Cell Biol. 2005;25:1696-712 pubmed
  33. Shibata M, Hattori H, Sasaki T, Gotoh J, Hamada J, Fukuuchi Y. Temporal profiles of the subcellular localization of Bim, a BH3-only protein, during middle cerebral artery occlusion in mice. J Cereb Blood Flow Metab. 2002;22:810-20 pubmed
    ..During MCAO, Bad did not show any change in phosphorylation state or subcellular localization.
  34. Dominov J, Houlihan Kawamoto C, Swap C, Miller J. Pro- and anti-apoptotic members of the Bcl-2 family in skeletal muscle: a distinct role for Bcl-2 in later stages of myogenesis. Dev Dyn. 2001;220:18-26 pubmed
    ..Both anti-apoptotic (Bcl-W, Bcl-X(L)) and pro-apoptotic (Bad, Bak, Bax) members of the Bcl-2 family were expressed in developing skeletal muscle in vivo...
  35. Hekman M, Albert S, Galmiche A, Rennefahrt U, Fueller J, Fischer A, et al. Reversible membrane interaction of BAD requires two C-terminal lipid binding domains in conjunction with 14-3-3 protein binding. J Biol Chem. 2006;281:17321-36 pubmed
    b>BAD is a Bcl-2 homology domain 3 (BH3)-only proapoptotic member of the Bcl-2 protein family that is regulated by phosphorylation in response to survival factors...
  36. Zimmerman M, Rahman N, Yang D, Lahat G, Lazar A, Pollock R, et al. Unphosphorylated STAT1 promotes sarcoma development through repressing expression of Fas and bad and conferring apoptotic resistance. Cancer Res. 2012;72:4724-32 pubmed publisher
    ..silencing of STAT1 in STS cells was sufficient to increase expression of the apoptotic mediators Fas and Bad and to elevate the sensitivity of STS cells to Fas-mediated apoptosis...
  37. Yang E, Zha J, Jockel J, Boise L, Thompson C, Korsmeyer S. Bad, a heterodimeric partner for Bcl-XL and Bcl-2, displaces Bax and promotes cell death. Cell. 1995;80:285-91 pubmed
    ..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...
  38. Polzien L, Baljuls A, Rennefahrt U, Fischer A, Schmitz W, Zahedi R, et al. Identification of novel in vivo phosphorylation sites of the human proapoptotic protein BAD: pore-forming activity of BAD is regulated by phosphorylation. J Biol Chem. 2009;284:28004-20 pubmed publisher
    b>BAD is a proapoptotic member of the Bcl-2 protein family that is regulated by phosphorylation in response to survival factors...
  39. Vicente Torres M, Schacht J. A BAD link to mitochondrial cell death in the cochlea of mice with noise-induced hearing loss. J Neurosci Res. 2006;83:1564-72 pubmed
    ..overload triggers mitochondria-mediated death pathways through activation of Bcl-2-associated death promoter (BAD) by calcineurin...
  40. Alejandro E, Johnson J. Inhibition of Raf-1 alters multiple downstream pathways to induce pancreatic beta-cell apoptosis. J Biol Chem. 2008;283:2407-17 pubmed
    ..An alternative Erk-independent pathway downstream of Raf-1 kinase involving the pro-apoptotic protein Bad has recently been characterized in other tissues...
  41. Fernandez E, Gustafson A, Andersson M, Hellman B, Dencker L. Cadmium-induced changes in apoptotic gene expression levels and DNA damage in mouse embryos are blocked by zinc. Toxicol Sci. 2003;76:162-70 pubmed
    ..The Bad transcripts did not change at any experimental condition...
  42. Yu C, Minemoto Y, Zhang J, Liu J, Tang F, Bui T, et al. JNK suppresses apoptosis via phosphorylation of the proapoptotic Bcl-2 family protein BAD. Mol Cell. 2004;13:329-40 pubmed
    ..for IL-3-mediated cell survival through phosphorylation and inactivation of the proapoptotic Bcl-2 family protein BAD. IL-3 withdrawal-induced apoptosis is promoted by inhibition of JNK but suppressed by expression of a ..
  43. Exley G, Tang C, McElhinny A, Warner C. Expression of caspase and BCL-2 apoptotic family members in mouse preimplantation embryos. Biol Reprod. 1999;61:231-9 pubmed
    ..This result supports a model in which the ratio of BCL-2 to BAX is altered in apoptotic embryos. ..
  44. Kelekar A, Chang B, Harlan J, Fesik S, Thompson C. Bad is a BH3 domain-containing protein that forms an inactivating dimer with Bcl-XL. Mol Cell Biol. 1997;17:7040-6 pubmed
    The Bcl-2 related protein Bad is a promoter of apoptosis and has been shown to dimerize with the anti-apoptotic proteins Bcl-2 and Bcl-XL. Overexpression of Bad in murine FL5...
  45. Fueller J, Becker M, Sienerth A, Fischer A, Hotz C, Galmiche A. C-RAF activation promotes BAD poly-ubiquitylation and turn-over by the proteasome. Biochem Biophys Res Commun. 2008;370:552-6 pubmed publisher
    b>BAD, a member of the BCL2 family, exhibits an original mode of regulation by phosphorylation. In the present report, we examine the role of the kinase C-RAF in this process...
  46. Hagen S, Yang D, Tashima K, Taylor N, Fox J. Epithelial cell expression of BCL-2 family proteins predicts mechanisms that regulate Helicobacter pylori-induced pathology in the mouse stomach. Lab Invest. 2008;88:1227-44 pubmed publisher
    ..This strategy identified BCL-2, BAK, and BAD as the major prosurvival and proapoptotic proteins, in surface cells and BAD as the only BCL-2 family protein ..
  47. Hassan S, Karpova Y, Baiz D, Yancey D, Pullikuth A, Flores A, et al. Behavioral stress accelerates prostate cancer development in mice. J Clin Invest. 2013;123:874-86 pubmed publisher
    ..antagonist ICI118,551 or by inducible expression of PKA inhibitor (PKI) or of BCL2-associated death promoter (BAD) with a mutated PKA phosphorylation site (BADS112A) in xenograft tumors...
  48. Putcha G, Harris C, Moulder K, Easton R, Thompson C, Johnson E. Intrinsic and extrinsic pathway signaling during neuronal apoptosis: lessons from the analysis of mutant mice. J Cell Biol. 2002;157:441-53 pubmed
    ..exhibit functional redundancy or compensatory expression, at least in the Bax-/-, Bak-/-, Bim-/-, Bid-/-, and Bad-/- neurons examined...
  49. Ekoff M, Kaufmann T, Engström M, Motoyama N, Villunger A, Jönsson J, et al. The BH3-only protein Puma plays an essential role in cytokine deprivation induced apoptosis of mast cells. Blood. 2007;110:3209-17 pubmed
    ..In this study we investigated the role of the BH3-only proteins Noxa, Bad, Bim, Bmf, Bid, and Puma in apoptosis of mucosal-like mast cells (MLMCs) and connective tissue-like mast cells (..
  50. Pongracz J, Parnell S, Anderson G, Jaffrezou J, Jenkinson E. Con A activates an Akt/PKB dependent survival mechanism to modulate TCR induced cell death in double positive thymocytes. Mol Immunol. 2003;39:1013-23 pubmed
    ..by Con A and not by alpha-CD3 epsilon decreases the gene and protein expression of the pro-apoptotic molecule, Bad; and that Con A is capable of the activation of the survival signalling pathway including protein kinase B (Akt/PKB)..
  51. Gimenez Cassina A, Martínez François J, Fisher J, Szlyk B, Polak K, Wiwczar J, et al. BAD-dependent regulation of fuel metabolism and K(ATP) channel activity confers resistance to epileptic seizures. Neuron. 2012;74:719-30 pubmed publisher
    ..We provide genetic evidence that BAD, a protein with dual functions in apoptosis and glucose metabolism, imparts reciprocal effects on metabolism of ..
  52. Torii S, Goto Y, Ishizawa T, Hoshi H, Goryo K, Yasumoto K, et al. Pro-apoptotic activity of inhibitory PAS domain protein (IPAS), a negative regulator of HIF-1, through binding to pro-survival Bcl-2 family proteins. Cell Death Differ. 2011;18:1711-25 pubmed publisher
    ..IPAS contributed to dysfunction of Bcl-x(L) by inhibiting the interaction of Bcl-x(L) with Bax. These results demonstrate that IPAS functions as a dual function protein involved in transcription repression and apoptosis. ..
  53. Berndtsson M, Konishi Y, Bonni A, Hägg M, Shoshan M, Linder S, et al. Phosphorylation of BAD at Ser-128 during mitosis and paclitaxel-induced apoptosis. FEBS Lett. 2005;579:3090-4 pubmed
    Phosphorylation of BCL-2 family member BAD at different residues triggers different physiological effects, either inhibiting or promoting apoptosis...
  54. Withers D, Burks D, Towery H, Altamuro S, Flint C, White M. Irs-2 coordinates Igf-1 receptor-mediated beta-cell development and peripheral insulin signalling. Nat Genet. 1999;23:32-40 pubmed
    ..Thus, Irs-2 integrates the effects of insulin in peripheral target tissues with Igf-1 in pancreatic beta-cells to maintain glucose homeostasis. ..
  55. Fischer S, Belz G, Strasser A. BH3-only protein Puma contributes to death of antigen-specific T cells during shutdown of an immune response to acute viral infection. Proc Natl Acad Sci U S A. 2008;105:3035-40 pubmed publisher
    ..After infection with human herpes simplex virus (HSV-1), mice lacking Noxa, Bid, or Bad had a normal increase and subsequent decline in the numbers of antigen-specific CD8(+) T cells...
  56. Götz R, Wiese S, Takayama S, Camarero G, Rossoll W, Schweizer U, et al. Bag1 is essential for differentiation and survival of hematopoietic and neuronal cells. Nat Neurosci. 2005;8:1169-78 pubmed
    ..with the disturbance of a tripartite complex formed by Akt, B-Raf and Bag1, in addition to the absence of Bad phosphorylation at Ser136...
  57. Reed J. Bcl-2 family proteins. Oncogene. 1998;17:3225-36 pubmed
  58. Gu Z, Wu J, Wang S, Suburu J, Chen H, Thomas M, et al. Polyunsaturated fatty acids affect the localization and signaling of PIP3/AKT in prostate cancer cells. Carcinogenesis. 2013;34:1968-75 pubmed publisher
    ..alters PI(3,4,5)P3 (PIP3) and phospho-AKT(S473) protein localization, decreases pPDPK1(S241)-AKT and AKT-BAD interaction and suppresses prostate tumor growth...
  59. Ness J, Harvey C, Strasser A, Bouillet P, Klocke B, Roth K. Selective involvement of BH3-only Bcl-2 family members Bim and Bad in neonatal hypoxia-ischemia. Brain Res. 2006;1099:150-9 pubmed
    ..The Bcl-2 protein family consists of both pro- (e.g. Bax, Bad, Bid, Bim) and anti-apoptotic (e.g...
  60. Llambi F, Wang Y, Victor B, Yang M, Schneider D, Gingras S, et al. BOK Is a Non-canonical BCL-2 Family Effector of Apoptosis Regulated by ER-Associated Degradation. Cell. 2016;165:421-33 pubmed publisher
    ..When proteasome function, VCP, or gp78 activity is compromised, BOK is stabilized to induce MOMP and apoptosis independently of other BCL-2 proteins. ..
  61. Gray D, Kupresanin F, Berzins S, Herold M, O Reilly L, Bouillet P, et al. The BH3-only proteins Bim and Puma cooperate to impose deletional tolerance of organ-specific antigens. Immunity. 2012;37:451-62 pubmed publisher
    ..Our data show that Puma cooperates with Bim to impose a thymic-deletion checkpoint to peripheral self-antigens and cement the notion that defects in apoptosis alone are sufficient to cause autoimmune disease. ..
  62. Zhang J, Liu J, Yu C, Lin A. BAD Ser128 is not phosphorylated by c-Jun NH2-terminal kinase for promoting apoptosis. Cancer Res. 2005;65:8372-8 pubmed
    The phosphorylation and regulation of the proapoptotic Bcl-2 family protein BAD by c-Jun NH2-terminal kinase (JNK) is controversial. JNK can suppress interleukin-3 withdrawal-induced apoptosis via phosphorylation of BAD at Thr201...
  63. Seo S, Chen Y, Ivanovska I, Ranger A, Hong S, Dawson V, et al. BAD is a pro-survival factor prior to activation of its pro-apoptotic function. J Biol Chem. 2004;279:42240-9 pubmed
    The mammalian BAD protein belongs to the BH3-only subgroup of the BCL-2 family. In contrast to its known pro-apoptotic function, we found that endogenous and overexpressed BAD(L) can inhibit cell death in neurons and other cell types...
  64. Du A, Hunter C, Murray J, Noble D, Cai C, Evans S, et al. Islet-1 is required for the maturation, proliferation, and survival of the endocrine pancreas. Diabetes. 2009;58:2059-69 pubmed publisher
    ..These results demonstrate the requirement for Isl-1 in the maturation, proliferation, and survival of the second wave of hormone-producing islet cells. ..
  65. Trécherel E, Godin C, Louandre C, Benchitrit J, Poirot S, Mazière J, et al. Upregulation of BAD, a pro-apoptotic protein of the BCL2 family, in vascular smooth muscle cells exposed to uremic conditions. Biochem Biophys Res Commun. 2012;417:479-83 pubmed publisher
    ..the existence of an alteration in expression and function of one pro-apoptotic member of this family, the protein BAD. We explore the regulation of BAD by uremic toxins and report the sensitization of vascular smooth muscle cells to ..
  66. Lu X, Kambe F, Cao X, Yoshida T, Ohmori S, Murakami K, et al. DHCR24-knockout embryonic fibroblasts are susceptible to serum withdrawal-induced apoptosis because of dysfunction of caveolae and insulin-Akt-Bad signaling. Endocrinology. 2006;147:3123-32 pubmed
    ..with a marked decrease in the intracellular and plasma membrane cholesterol levels, Akt inactivation, and Bad dephosphorylation...
  67. Rucker E, Dierisseau P, Wagner K, Garrett L, Wynshaw Boris A, Flaws J, et al. Bcl-x and Bax regulate mouse primordial germ cell survival and apoptosis during embryogenesis. Mol Endocrinol. 2000;14:1038-52 pubmed
    ..These findings demonstrate that the balance of Bcl-x and Bax control PGC survival and apoptosis. ..
  68. Subramanian R, Masters S, Zhang H, Fu H. Functional conservation of 14-3-3 isoforms in inhibiting bad-induced apoptosis. Exp Cell Res. 2001;271:142-51 pubmed
    ..Here we report that multiple isoforms of 14-3-3 proteins were capable of binding to several ligands, Bad, Raf-1, and Cbl...
  69. Jin S, Zhuo Y, Guo W, Field J. p21-activated Kinase 1 (Pak1)-dependent phosphorylation of Raf-1 regulates its mitochondrial localization, phosphorylation of BAD, and Bcl-2 association. J Biol Chem. 2005;280:24698-705 pubmed
    ..of its signals to MEK and ERK, by translocating to the mitochondria where it binds Bcl-2 and displaces BAD. However, the answer to the question of how Raf-1 is normally lured to the mitochondria and becomes activated ..
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