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Human cytomegalovirus protein UL38 inhibits host cell stress responses by antagonizing the tuberous sclerosis protein complex. Cell Host Microbe 2008 Apr 17;3(4):253-62

Date

04/15/2008

Pubmed ID

18407068

Pubmed Central ID

PMC2759192

DOI

10.1016/j.chom.2008.03.002

Scopus ID

2-s2.0-41849101685 (requires institutional sign-in at Scopus site)   174 Citations

Abstract

Human cytomegalovirus proteins alter host cells to favor virus replication. These viral proteins include pUL38, which prevents apoptosis. To characterize the mode of action of pUL38, we modified the viral genome to encode an epitope-tagged pUL38 and used rapid immunoaffinity purification to isolate pUL38-interacting host proteins, which were then identified by mass spectrometry. One of the cellular proteins identified was TSC2, a constituent of the tuberous sclerosis tumor suppressor protein complex (TSC1/2). TSC1/2 integrates stress signals and regulates the mammalian target of rapamycin complex 1 (mTORC1), a protein complex that responds to stress by limiting protein synthesis and cell growth. We showed that pUL38 interacts with TSC1 and TSC2 in cells infected with wild-type cytomegalovirus. Furthermore, TSC1/2 failed to regulate mTORC1 in cells expressing pUL38, and these cells exhibited the enlarged size characteristic of cytomegalovirus infection. Thus, pUL38 supports virus replication at least in part by blocking cellular responses to stress.

Author List

Moorman NJ, Cristea IM, Terhune SS, Rout MP, Chait BT, Shenk T

Author

Scott Terhune PhD Professor in the Microbiology and Immunology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Capsid Proteins
Cells, Cultured
Cytomegalovirus
Cytomegalovirus Infections
Down-Regulation
Fibroblasts
Genes, Tumor Suppressor
Heat-Shock Proteins
Humans
Mechanistic Target of Rapamycin Complex 1
Multiprotein Complexes
Proteins
Signal Transduction
TOR Serine-Threonine Kinases
Transcription Factors
Tumor Suppressor Proteins
Virus Replication