An adenovirus inhibitor of tumor necrosis factor alpha-induced apoptosis complexes with dynein and a small GTPase.
Adenoviruses (Ad) code for immunoregulatory and cytokine regulatory proteins, one of which is the early region 3, 14.7-kDa protein (Ad E3-14.7K), which has been shown to inhibit tumor necrosis factor alpha-induced apoptosis. In an effort to understand the mechanism of action of Ad E3-14.7K, we previously searched for cell proteins with which it interacted. Three Ad E3-14.7K-interacting proteins (FIP-1, -2, and -3) were isolated. FIP-1 is a small GTPase which was used in this report as bait in the yeast two-hybrid system to find other interacting cell targets. The search resulted in the isolation of a protein, which we called GIP-1 (GTPase-interacting protein) that subsequently was shown to be identical to one of the light-chain components of human dynein (TCTEL1). FIP-1 was able to bind both TCTEL1 and Ad E3-14.7K simultaneously and was necessary to form a complex in which the viral protein was associated with a microtubule-binding motor protein. The functional significance of these interactions is discussed with respect to the steps of the Ad life cycle which are microtubule associated.
Lukashok
S A
SA
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Tarassishin
L
L
Li
Y
Y
Horwitz
M S
MS
D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D017503:Adenovirus E3 Proteins / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D017209:Apoptosis; D002352:Carrier Proteins / Q000378:metabolism; D002453:Cell Cycle; D002460:Cell Line; D004398:Dyneins / Q000737:chemistry / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008868:Microtubule Proteins / Q000235:genetics / Q000378:metabolism; D008869:Microtubule-Associated Proteins; D008969:Molecular Sequence Data; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism; D009687:Nuclear Proteins; D010957:Plasmids / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D020798:Two-Hybrid System Techniques; D056427:t-Complex Genome Region
D017503:Adenovirus E3 Proteins; D002352:Carrier Proteins; C533376:DYNLT1 protein, human; D008868:Microtubule Proteins; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D020558:GTP Phosphohydrolases; D004398:Dyneins; D020559:Monomeric GTP-Binding Proteins