Enhanced apoptosis by a novel gene, Bak-like, that lacks the BH3 domain.
In a variety of physiological settings, cells are eliminated by apoptosis-a genetically encoded process of cellular suicide. Bak, a member of the Bcl-2 protein family, accelerates apoptosis by an unknown mechanism. We have found a novel cDNA encoding a 101-amino acid protein that possesses a Bak-like sequence in our full-length cDNA bank and termed it Bak-like. This protein shares the conserved domains BH1 and BH2 with other pro-apoptotic proteins, but lacks the BH3 domain. Database searches identified this gene on chromosome 6, which could account for the cloned bak and bak-like transcripts by alternative splicing. Bak-like is expressed in a wide variety of tissues. Bak-like is different from bak by Southern blots using probes with or without homology to bak. Despite the loss of the BH3 sequence, bak-like did enhance apoptosis, but was less potent than bak. Confocal microscopy of HeLa cells revealed that EGFP-Bak-like was located diffusely throughout the cytosol. However, upon induction of apoptosis, EGFP-Bak-like redistributed into a punctuate pattern, colocalizing with mitochondria. Like bak, the bak-like gene product directly enhanced apoptotic cell death following an appropriate stimulus.
Kim
Jin Kyeoung
JK
Graduate School of Life science and Biotechnology, College of Medicine, Pochon CHA University, Seoul 135-081, Republic of Korea.
Kim
Kye Seong
KS
Ahn
Jung Yong
JY
Kim
Nam Keun
NK
Chung
Hyung Min
HM
Yun
Hwan Jung
HJ
Cha
Kwang Yul
KY
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D015723:Gene Library; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000378:metabolism; D016415:Sequence Alignment; D050998:bcl-2 Homologous Antagonist-Killer Protein
C494772:BAK1 protein, human; C494773:Bak1 protein, mouse; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D050998:bcl-2 Homologous Antagonist-Killer Protein