Adenovirus E1B 19-kDa death suppressor protein interacts with Bax but not with Bad.
Adenovirus E1B 19-kDa protein (19K) is a member of the Bcl-2 family of suppressors of apoptosis. The suppressors function through heterodimerization with the death promoters, Bax and related proteins, thus establishing a set point within the cell that determines whether or not apoptosis is executed in response to a death signal. Sequence similarities between 19K and Bcl-2 are largely restricted to short Bcl-2 homology (BH) domains that mediate interaction with Bax. The BH1 sequence in 19K is degenerate but nevertheless contains a conserved glycine residue found in all family members that when mutated to alanine in Bcl-2 results in loss of Bcl-2 function and ability to dimerize with Bax (Yin, X.-M., Oltvai, Z. N., and Korsmeyer, S. J. (1994) Nature 369, 321-323). Here, we show that the analogous mutation in BH1 of 19K also abrogates the anti-apoptotic properties of 19K and its ability to interact with Bax, thus establishing the critical importance of this residue within BH1 and the likely similarity of Bcl-2 and 19K function. In distinct contrast to Bcl-2, however, 19K interaction was not detected with Bad, a Bcl-2/Bcl-XL dimerizing protein that can potentially regulate a Bax middle dotBcl-2/Bcl-XL survival set point and reinstate susceptibility to a death signal. Furthermore, the anti-apoptotic function of 19K was not overcome by enforced expression of Bad in transfected cells. This feature of 19K may provide adenovirus with a selective advantage in evading premature induction of apoptosis by the host cell.
Chen
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Department of Biochemistry, McIntyre Medical Sciences Building, McGill University, Montreal, Quebec, Canada H3G 1Y6.
Branton
P E
PE
Yang
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E
Korsmeyer
S J
SJ
Shore
G C
GC
D017501:Adenovirus E1B Proteins / Q000378:metabolism*; D000260:Adenoviruses, Human / Q000235:genetics*; D000818:Animals; D017209:Apoptosis; D001665:Binding Sites; D016466:CHO Cells; D002352:Carrier Proteins / Q000378:metabolism*; D006224:Cricetinae; D006801:Humans; D051379:Mice; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011994:Recombinant Proteins; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein
D017501:Adenovirus E1B Proteins; C494819:BAD protein, human; C494826:BAX protein, human; C494820:Bad protein, mouse; C494827:Bax protein, mouse; D002352:Carrier Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein