Distinct requirements of adenovirus E1b55K protein for degradation of cellular substrates.

Distinct requirements of adenovirus E1b55K protein for degradation of cellular substrates. Research Abstract Details 

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Distinct requirements of adenovirus E1b55K protein for degradation of cellular substrates. Abstract Text:

The E1b55K and E4orf6 proteins of adenovirus type 5 (Ad5) assemble into a complex together with cellular proteins including cullin 5, elongins B and C, and Rbx1. This complex possesses E3 ubiquitin ligase activity and targets cellular proteins for proteasome-mediated degradation. The ligase activity has been suggested to be responsible for all functions of E1b55K/E4orf6, including promoting efficient viral DNA replication, preventing a cellular DNA damage response, and stimulating late viral mRNA nuclear export and late protein synthesis. The known cellular substrates for degradation by E1b55K/E4orf6 are the Mre11/Rad50/Nbs1 DNA repair complex, the tumor suppressor p53, and DNA ligase IV. Here we show that the degradation of individual targets can occur independently of other substrates. Furthermore, we identify separation-of-function mutant forms of E1b55K that can distinguish substrates for binding and degradation. Our results identify distinct regions of E1b55K that are involved in substrate recognition but also imply that there are additional requirements beyond protein association. These mutant proteins will facilitate the determination of the relevance of specific substrates to the functions of E1b55K in promoting infection and inactivating host defenses.

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Distinct requirements of adenovirus E1b55K protein for degradation of cellular substrates. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of virology

VOLUME: 82

Page Numbers: 9043-55

Journal Abbreviation: J. Virol.

ISSN: 1098-5514

DAY: 9

MONTH: 07

YEAR: 2008

Distinct requirements of adenovirus E1b55K protein for degradation of cellular substrates. Information

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LANGUAGE: eng

NlmUniqueID: 113724

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Grant and Affiliation Information for Distinct requirements of adenovirus E1b55K protein for degradation of cellular substrates.

AFFILIATION: Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.

Country: United States

AGENCY: United States NCI

GRANT: CA97093

ACRONYM: CA

MEDLINETA: J Virol

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