This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Feng, P. Articles by Jung, J. U. Search for Related Content PubMed PubMed Citation Articles by Feng, P. Articles by Jung, J. U.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, May 2004, p. 3938-3948, Vol. 24, No. 9
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.9.3938-3948.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Kaposi's Sarcoma-Associated Herpesvirus K7 Protein Targets a Ubiquitin-Like/Ubiquitin-Associated Domain-Containing Protein To Promote Protein Degradation

Pinghui Feng,¹ Christopher W. Scott,¹ Nam-Hyuk Cho,¹ Hiroyuki Nakamura,^1,2 Young-Hwa Chung,¹ Mervyn J. Monteiro,³ and Jae U. Jung^1*

Department of Microbiology and Molecular Genetics and Tumor Virology Division, New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772,¹ Department of Infectious Diseases, National Research Institute for Child Health and Development, Setagaya-ku, Tokyo 154-8567, Japan,² Department of Neurology, Medical Biotechnology Center, University of Maryland Biotechnology Institute, Baltimore, Maryland 21201³

Received 20 November 2003/ Returned for modification 12 January 2004/ Accepted 6 February 2004

Pathogens exploit host machinery to establish an environment that favors their propagation. Because of their pivotal roles in cellular physiology, protein degradation pathways are common targets for viral proteins. Protein-linking integrin-associated protein and cytoskeleton 1 (PLIC1), also called ubiquilin, contains an amino-terminal ubiquitin-like (UBL) domain and a carboxy-terminal ubiquitin-associated (UBA) domain. PLIC1 is proposed to function as a regulator of the ubiquitination complex and proteasome machinery. Kaposi's sarcoma-associated herpesvirus (KSHV) contains a small membrane protein, K7, that protects cells from apoptosis induced by various stimuli. We report here that cellular PLIC1 is a K7-interacting protein and that the central hydrophobic region of K7 and the carboxy-terminal UBA domain of PLIC1 are responsible for their interaction. Cellular PLIC1 formed a dimer and bound efficiently to polyubiquitinated proteins through its carboxy-terminal UBA domain, and this activity correlated with its ability to stabilize cellular IB protein. In contrast, K7 interaction prevented PLIC1 from forming a dimer and binding to polyubiquitinated proteins, leading to the rapid degradation of IB. Furthermore, K7 expression promoted efficient degradation of the p53 tumor suppressor, resulting in inhibition of p53-mediated apoptosis. These results indicate that KSHV K7 targets a regulator of the ubiquitin- and proteasome-mediated degradation machinery to deregulate cellular protein turnover, which potentially provides a favorable environment for viral reproduction.

---

* Corresponding author. Mailing address: Tumor Virology Division, New England Primate Research Center, Harvard Medical School, P.O. Box 9102, 1 Pine Hill Dr., Southborough, MA 01772-9102. Phone: (508) 624-8083. Fax: (508) 786-1416. E-mail: jae_jung{at}hms.harvard.edu.

---

Molecular and Cellular Biology, May 2004, p. 3938-3948, Vol. 24, No. 9
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.9.3938-3948.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Kim, S. H., Shi, Y., Hanson, K. A., Williams, L. M., Sakasai, R., Bowler, M. J., Tibbetts, R. S. (2009). Potentiation of Amyotrophic Lateral Sclerosis (ALS)-associated TDP-43 Aggregation by the Proteasome-targeting Factor, Ubiquilin 1. J. Biol. Chem. 284: 8083-8092 [Abstract] [Full Text]  
• Ficklin, M. B., Zhao, S., Feng, G. (2005). Ubiquilin-1 Regulates Nicotine-induced Up-regulation of Neuronal Nicotinic Acetylcholine Receptors. J. Biol. Chem. 280: 34088-34095 [Abstract] [Full Text]