Bcl-G, a Novel Pro-apoptotic Member of the Bcl-2 Family*

A new member of the Bcl-2 family was identified, Bcl-G. The human BCL-G gene consists of 6 exons, resides on chromosome 12p12, and encodes two proteins through alternative mRNA splicing, Bcl-GL (long) and Bcl-GS (short) consisting of 327 and 252 amino acids in length, respectively. Bcl-GL and Bcl-GS have identical sequences for the first 226 amino acids but diverge thereafter. Among the Bcl-2 homology (BH) domains previously recognized in Bcl-2 family proteins, the BH3 domain is found in both Bcl-GL and Bcl-GS, but only the longer Bcl-GL protein possesses a BH2 domain. Bcl-GLmRNA is expressed widely in adult human tissues, whereas Bcl-GS mRNA was found only in testis. Overexpression of Bcl-GL or Bcl-GS in cells induced apoptosis although Bcl-GS was far more potent than Bcl-GL. Apoptosis induction by Bcl-GS depended on the BH3 domain and was suppressed by coexpression of anti-apoptotic Bcl-XL protein. Bcl-XL also coimmunoprecipitated with Bcl-GS but not with mutants of Bcl-GS in which the BH3 domain was deleted or mutated or with Bcl-GL. Bcl-GS was predominantly localized to cytosolic organelles, whereas Bcl-GL was diffusely distributed throughout the cytosol. A mutant of Bcl-GL in which the BH2 domain was deleted displayed increased apoptotic activity and coimmunoprecipitated with Bcl-XL, suggesting that the BH2 domain autorepresses Bcl-GL.

[1]  R. Craig,et al.  Exon Skipping in Mcl-1 Results in a Bcl-2 Homology Domain 3 Only Gene Product That Promotes Cell Death* , 2000, The Journal of Biological Chemistry.

[2]  T. Taniguchi,et al.  Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis. , 2000, Science.

[3]  Guido Kroemer,et al.  Mitochondrial control of cell death , 2000, Nature Medicine.

[4]  T. Yanagida,et al.  Electrophysiological Study of a Novel Large Pore Formed by Bax and the Voltage-dependent Anion Channel That Is Permeable to Cytochrome c * , 2000, The Journal of Biological Chemistry.

[5]  A. Godzik,et al.  BAR: An apoptosis regulator at the intersection of caspases and Bcl-2 family proteins. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[6]  A. Strasser,et al.  Proapoptotic Bcl-2 relative Bim required for certain apoptotic responses, leukocyte homeostasis, and to preclude autoimmunity. , 1999, Science.

[7]  S. R. Datta,et al.  Cellular survival: a play in three Akts. , 1999, Genes & development.

[8]  S. Korsmeyer,et al.  Bid-deficient mice are resistant to Fas-induced hepatocellular apoptosis , 1999, Nature.

[9]  S. Korsmeyer,et al.  BCL-2 family members and the mitochondria in apoptosis. , 1999, Genes & development.

[10]  A. Strasser,et al.  The proapoptotic activity of the Bcl-2 family member Bim is regulated by interaction with the dynein motor complex. , 1999, Molecular cell.

[11]  John C Reed,et al.  Bcl-2 family proteins , 1998, Oncogene.

[12]  S. Korsmeyer,et al.  Mutagenesis of the BH3 Domain of BAX Identifies Residues Critical for Dimerization and Killing , 1998, Molecular and Cellular Biology.

[13]  J C Reed,et al.  Mitochondria and apoptosis. , 1998, Science.

[14]  S. Cory,et al.  The Bcl-2 protein family: arbiters of cell survival. , 1998, Science.

[15]  Junying Yuan,et al.  Cleavage of BID by Caspase 8 Mediates the Mitochondrial Damage in the Fas Pathway of Apoptosis , 1998, Cell.

[16]  Xiaodong Wang,et al.  Bid, a Bcl2 Interacting Protein, Mediates Cytochrome c Release from Mitochondria in Response to Activation of Cell Surface Death Receptors , 1998, Cell.

[17]  C. Thompson,et al.  Bcl-2-family proteins: the role of the BH3 domain in apoptosis. , 1998, Trends in cell biology.

[18]  D. Vaux,et al.  Cell death: Shadow Baxing , 1998, Current Biology.

[19]  John Calvin Reed,et al.  Bcl-2 family proteins as ion-channels , 1998, Cell Death and Differentiation.

[20]  John Calvin Reed,et al.  Bax inhibitor-1, a mammalian apoptosis suppressor identified by functional screening in yeast. , 1998, Molecular cell.

[21]  M. Hengartner.  Apoptosis: Death cycle and Swiss army knives , 1998, Nature.

[22]  A. Strasser,et al.  Bim: a novel member of the Bcl‐2 family that promotes apoptosis , 1998, The EMBO journal.

[23]  J. Díaz,et al.  Dimerization Properties of Human BAD , 1997, The Journal of Biological Chemistry.

[24]  S. Fesik,et al.  Bad is a BH3 domain-containing protein that forms an inactivating dimer with Bcl-XL , 1997, Molecular and cellular biology.

[25]  Yi-Te Hsu,et al.  Movement of Bax from the Cytosol to Mitochondria during Apoptosis , 1997, The Journal of cell biology.

[26]  G Waksman,et al.  Comparison of the ion channel characteristics of proapoptotic BAX and antiapoptotic BCL-2. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[27]  S. Korsmeyer,et al.  BH3 Domain of BAD Is Required for Heterodimerization with BCL-XL and Pro-apoptotic Activity* , 1997, The Journal of Biological Chemistry.

[28]  F Gambale,et al.  Inhibition of Bax channel-forming activity by Bcl-2. , 1997, Science.

[29]  John Calvin Reed.  Double identity for proteins of the Bcl-2 family , 1997, Nature.

[30]  R. Meadows,et al.  Structure of Bcl-xL-Bak Peptide Complex: Recognition Between Regulators of Apoptosis , 1997, Science.

[31]  John Calvin Reed,et al.  Structure-function comparisons of the proapoptotic protein Bax in yeast and mammalian cells , 1996, Molecular and cellular biology.

[32]  L. Hennighausen,et al.  Bax and Bcl-xS are induced at the onset of apoptosis in involuting mammary epithelial cells , 1996, Mechanisms of Development.

[33]  S. Korsmeyer,et al.  Bax-Deficient Mice with Lymphoid Hyperplasia and Male Germ Cell Death , 1995, Science.

[34]  al. et,et al.  Massive cell death of immature hematopoietic cells and neurons in Bcl-x-deficient mice , 1995, Science.

[35]  S. Korsmeyer,et al.  Bcl-2-deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys, and hypopigmented hair , 1993, Cell.

[36]  C. Thompson,et al.  bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death , 1993, Cell.

[37]  S. Korsmeyer,et al.  Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programed cell death , 1993, Cell.

[38]  Y. Tsujimoto,et al.  Analysis of the structure, transcripts, and protein products of bcl-2, the gene involved in human follicular lymphoma. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[39]  D. Sinnett,et al.  Childhood acute lymphoblastic leukemia: is there a tumor suppressor gene in chromosome 12p12.3? , 1999, Leukemia & lymphoma.

[40]  J. Yokota,et al.  Ovarian cancer has frequent loss of heterozygosity at chromosome 12p12.3-13.1 (region of TEL and Kip1 loci) and chromosome 12q23-ter: evidence for two new tumour-suppressor genes. , 1997, British Journal of Cancer.