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The Kaposi's sarcoma-associated herpesvirus K5 E3 ubiquitin ligase modulates targets by multiple molecular mechanisms.

The Kaposi's sarcoma-associated herpesvirus K5 E3 ubiquitin ligase modulates targets by multiple molecular mechanisms. Research Abstract Details 

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  • The Kaposi's sarcoma-associated herpesvirus K5 E3 ubiquitin ligase modulates targets by multiple molecular mechanisms. Abstract Text:

    robert e meansRobert E Means,sabine m langSabine M Lang,jae u jungJae U Jung,

    Kaposi's sarcoma-associated herpesvirus encodes two highly related membrane-associated, RING-CH-containing (MARCH) family E3 ubiquitin ligases, K3 and K5, that can down regulate a variety of cell surface proteins through enhancement of their endocytosis and degradation. In this report we present data that while K5 modulation of major histocompatibility complex class I (MHC-I) closely mirrors the mechanisms used by K3, alternative molecular pathways are utilized by this E3 ligase in the down regulation of intercellular adhesion molecule 1 (ICAM-1) and B7.2. Internalization assays demonstrate that down regulation of each target can occur through increased endocytosis from the cell surface. However, mutation of a conserved tyrosine-based endocytosis motif in K5 resulted in a protein lacking the ability to direct an increased rate of MHC-I or ICAM-1 internalization but still able to down regulate B7.2 in a ubiquitin-dependent but endocytosis-independent manner. Further, mutation of two acidic clusters abolished K5-mediated MHC-I degradation while only slightly decreasing ICAM-1 or B7.2 protein destruction. This same mutant abolished detectable ubiquitylation of all targets. These data indicate that while K5 can act as an E3 ubiquitin ligase to directly mediate cell surface molecule destruction, regulation of its targets occurs through multiple pathways, including ubiquitin-independent mechanisms.

    The Kaposi's sarcoma-associated herpesvirus K5 E3 ubiquitin ligase modulates targets by multiple molecular mechanisms. Publishing Authors By Initials

    re meansRE Means,sm langSM Lang,ju jungJU Jung,

    For similar enzymes and coenzymes: enzymes: ligases: ubiquitin-protein ligase complexes: ubiquitin-protein ligases research abstracts see: enzymes and coenzymes: enzymes: ligases: ubiquitin-protein ligase complexes: ubiquitin-protein ligases research

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    The Kaposi's sarcoma-associated herpesvirus K5 E3 ubiquitin ligase modulates targets by multiple molecular mechanisms. Journal Published:

    PUBLICATION TYPE: Research Support, N.I.H., Extr

    Journal: Journal of virology

    VOLUME: 81

    Page Numbers: 6573-83

    Journal Abbreviation: J. Virol.

    ISSN: 0022-538X

    DAY: 4

    MONTH: 04

    YEAR: 2007

    The Kaposi's sarcoma-associated herpesvirus K5 E3 ubiquitin ligase modulates targets by multiple molecular mechanisms. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 113724

    The Kaposi's sarcoma-associated herpesvirus K5 E3 ubiquitin ligase modulates targets by multiple molecular mechanisms. Keywords Mesh Terms:

    KEYWORDS: Ubiquitin-Protein Ligases

    MESH TERMS: chemistry

    Chemical & Substance for Abstract: The Kaposi's sarcoma-associated herpesvirus K5 E3 ubiquitin ligase modulates targets by multiple molecular mechanisms. Information

    Substance Name: Ubiquitin-Protein Ligases

    Registry Number: EC 6.3.2.19

    Grant and Affiliation Information for The Kaposi's sarcoma-associated herpesvirus K5 E3 ubiquitin ligase modulates targets by multiple molecular mechanisms.

    AFFILIATION: Department of Pathology, Yale University School of Medicine, P.O. Box 208023, New Haven, CT 06520, USA. Robert.Means@Yale.edu

    Country: United States

    United States Research PublicationUnited States Research Publication

    AGENCY: United States NCI

    GRANT: R21 CA102535

    ACRONYM: CA

    MEDLINETA: J Virol

    REFSOURCE:

    DATABASENAME:

    ACCESSION NUMBER:

    Number Hits: 0

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