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Journal of Virology, May 2000, p. 4705-4709, Vol. 74, No. 10
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

An Adenovirus Inhibitor of Tumor Necrosis Factor Alpha-Induced Apoptosis Complexes with Dynein and a Small GTPase

Sophie A. Lukashok,dagger Leonid Tarassishin, Yongan Li,Dagger and Marshall S. Horwitz*

Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461

Received 18 November 1999/Accepted 24 February 2000

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.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461. Phone: (718) 430-2230 or -2083. Fax: (718) 430-8702. E-mail: horwitz{at}aecom.yu.edu.

dagger Present address: Emory University, Atlanta, Ga.

Dagger Present address: Glaxo Wellcome, Research Triangle Park, N.C.

Journal of Virology, May 2000, p. 4705-4709, Vol. 74, No. 10
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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