Abstract
Recent data on gene deletion analyses revealed that cells derived from animals that are deficient in both Bax and Bak (two key members of the “multidomain” proapoptotic Bcl-2 subfamily), but not cells lacking one of the two genes, are completely resistant to apoptotic death triggered by diverse stimuli. These data suggest that engagement of a “multidomain” proapoptotic member, BAX or BAK, is essential for apoptotic signaling. To gain further understanding of the molecular functions of the “multidomain” proapoptotic molecules, we used yeast two hybrid screen to identify protein partners of BAX. A proapoptotic protein, termed MAP-1 (Modulator of Apoptosis), was identified as a BAX-interacting protein from a human brain cDNA library. MAP-1 is a member of a growing family of proteins that were initially identified as onconeural antigens. MAP-1 contains a BH3-like motif and mediates caspase-dependent death in mammalian cells when overexpressed. Mutagenesis analyses revealed that the BH3-like domain of MAP-1 is required for association with BAX and for mediating apoptosis. Interestingly, in contrast to all other previously identified BAX-associating proteins that require only one of the three BH domains of BAX for binding, all the three BH (BH1, BH2 and BH3) domains of BAX are necessary for binding to MAP-1. Taken together, these data suggest that MAP-1 may mediate its proapoptotic function by engaging its BH3-like domain in binding the Bc1-XL-like hydrophobic pocket of BAX.
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References
Adams, J.M. and Cory, S. (1998). The Bcl-2 protein family: arbiters of cell survival. Science 281: 1322–1326.
Chan, S.L., Tan, K.O., Zhang, L., Yee, K.S., Ronca, F., Chan, M.Y., and Yu, V.C. (1999). FlAalpha, a death receptor-binding protein homologous to the Caenorhabditis elegans sex-determining protein, FEM-1, is a caspase substrate that mediates apoptosis. J. Biol. Chem. 274: 32461–32468.
Chan, S.L., Yee, K.S., Tan, K.M., and Yu, V.C. (2000). The Caenorhabditis elegans sex determination protein FEM-1 is a CED-3 substrate that associates with CED-4 and mediates apoptosis in mammalian cells. J. Biol. Chem. 275: 17925–17928.
Dalmau, J., Gultekin, S.H., Voltz, R., Hoard, R., DesChamps, T., Balmaceda, C., Batchelor, T., Gerstner, E., Eichen, J., Frennier, J., Posner, J.B., and Rosenfeld, M.R. (1999). Mal, a novel neuron-and testis-specific protein, is recognized by the serum of patients with paraneoplastic neurological disorders. Brain 122: 27–39.
Green, D.R., and Reed, J.C. (1998). Mitochondria and apoptosis. Science 281: 1309–1312.
Kelekar, A., and Thompson, C.B. (1998). BcI-2-family proteins: the role of the BH3 domain in apoptosis. Trends Cell Biol. 8: 324–330.
Lindsten, T., Ross, A.J., King, A., Zong, W.X., Rathmell, J.C., Shiels, H.A., Ulrich, E., Waymire, K.G., Mahar, P., Frauwirth, K., Chen, Y., Wei, M., Eng, V.M., Adelman, D.M., Simon, M.C., Ma, A., Golden, J.A., Evan, G., Korsmeyer, S.J., MacGregor, G.R., and Thompson, C.B. (2000). The combined functions of proapoptotic Bcl-2 family members bak and bax are essential for normal development of multiple tissues. Mol. Cell 6: 1389–1399.
Muchmore, S.W., Sattler, M., Liang, H., Meadows, R.P., Harlan, J.E., Yoon, H.S., Nettesheim, D., Chang, B.S., Thompson, C.B., Wong, S.L., Ng, S.L., and Fesik, S.W. (1996). X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed cell death. Nature 381: 335–341.
Ronca, E, Chan, S.L., and Yu, V.C. (1997). 1-(5-Isoquinolinesulfonyl)-2-methylpiperazine induces apoptosis in human neuroblastoma cells, SH-SY5Y, through a p53-dependent pathway. J. Biol. Chem. 272: 42524260.
Rosenfeld, M.R., Eichen, J.G., Wade, D.F., Posner, J.B., and Dalmau, J. (2001). Molecular and clinical diversity in paraneoplastic immunity to Ma proteins. Ann. Neurol. 50: 339–348.
Sattler, M., Liang, H., Nettesheim, D., Meadows, R.P., Harlan, J.E., Eberstadt, M., Yoon, H.S., Shuker, S.B., Chang, B.S., Minn, A.J., Thompson, C.B., and Fesik, S.W. (1997). Structure of Bc1-xL-Bak peptide complex: recognition between regulators of apoptosis. Science 275: 983–986.
Suzuki, M., Youle, R.J., and Tjandra, N. (2000). Structure of Bax: coregulation of dimer formation and intracellular localization. Cell 103: 645–654.
Tan, K.O., Tan, K.M., and Yu, V.C. (1999). A novel BH3-like domain in BID is required for intramolecular interaction and autoinhibition of pro-apoptotic activity. J. Biol. Chem. 274: 23687–23690.
Tan, K.O., Tan, K.M., Chan, S.L., Yee, K.S., Bevort, M., Ang, K.C., and Yu, V.C. (2001). MAP-1, a novel proapoptotic protein containing a BH3-like motif that associates with Bax through its Bc1–2 homology domains. J. Biol Chem. 276: 2802–2807.
Tsujimoto, Y. and Shimizu, S. (2000). Bc1–2 family: life-or-death switch. FEBS Lett. 466: 6–10.
Voltz, R., Gultekin, S.H., Rosenfeld, M.R., Gerstner, E., Eichen, J., Posner, J.B., and Dalmau, J. (1999). A serologic marker of paraneoplastic limbic and brain-stem encephalitis in patients with testicular cancer. N. Engl. J. Med. 340: 1788–1795.
Wang, K., Yin, X.M., Chao, D.T., Milliman, Cl., and Korsmeyer, S.J. (1996). BID: a novel BH3 domain-only death agonist. Genes Dev. 10: 2859–2869.
Wang, K., Gross, A., Waksman, G., and Korsmeyer, S.J. (1998). Mutagenesis of the BH3 domain of BAX identifies residues critical for dimerization and killing. Mol. Cell Biol. 18: 6083–6089.
Wei, M.C., Zong, W.X., Cheng, E.H., Lindsten, T., Panoutsakopoulou, V., Ross, A.J., Roth, K.A., MacGregor, G.R., Thompson, C.B., and Korsmeyer, S.J. (2001). Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science 292: 727–730.
Yin, X.M., Oltvai, Z.N., and Korsmeyer, S.J. (1994). BH1 and BH2 domains of Bcl-2 are required for inhibition of apoptosis and heterodimerization with Bax. Nature 369: 321–323.
Zha, H., Fisk, H.A., Yaffe, M.P., Mahajan, N., Herman, B., and Reed, J.C. (1996). Structure-function comparisons of the proapoptotic protein Bax in yeast and mammalian cells. Mol. Cell Biol. 16: 6494–6508.
Zha, J., Harada, H., Osipov, K., Jockel, J., Waksman, G., and Korsmeyer, S.J. (1997). BH3 domain of BAD is required for heterodimerization with BCL-XL andproapoptotic activity. J. Biol. Chem. 272: 2410124104.
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Tan, K.O., Chan, SL., Fu, N., Yu, V.C. (2003). MAP-1 Is a Putative Ligand for the Multidomain Proapoptotic Protein Bax. In: Shi, Y., Cidlowski, J.A., Scott, D., Wu, JR., Shi, YB. (eds) Molecular Mechanisms of Programmed Cell Death. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-5890-0_11
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DOI: https://doi.org/10.1007/978-1-4757-5890-0_11
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