Journal
CELL HOST & MICROBE
Volume 3, Issue 4, Pages 253-262Publisher
CELL PRESS
DOI: 10.1016/j.chom.2008.03.002
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Funding
- NCI NIH HHS [CA89810, R33 CA089810, R01 CA082396, R01 CA085786-09, R01 CA085786-08, CA85786, R01 CA085786-07, R01 CA085786] Funding Source: Medline
- NCRR NIH HHS [RR00862, RR22220, U54 RR022220, P41 RR000862] Funding Source: Medline
- NIAID NIH HHS [R01 AI054430, AI54430] Funding Source: Medline
- NIDA NIH HHS [DP1 DA026192] Funding Source: Medline
- NIGMS NIH HHS [GM62427, R01 GM062427] Funding Source: Medline
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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.
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