Gene interactions and pathways from curated databases and text-mining
Cell Host Microbe 2008, PMID: 18407068

Human cytomegalovirus protein UL38 inhibits host cell stress responses by antagonizing the tuberous sclerosis protein complex.

Moorman, Nathaniel J; Cristea, Ileana M; Terhune, Scott S; Rout, Michael P; Chait, Brian T; Shenk, Thomas

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.

Diseases/Pathways annotated by Medline MESH: Cytomegalovirus Infections
Document information provided by NCBI PubMed

Text Mining Data

mammalian target of rapamycin → 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 "

Manually curated Databases

No curated data.