The murine gamma -herpesvirus-68 K3 (MK3) is a PHD/LAP finger protein that downregulates major histocompatibility complex (MHC) class I expression. In transfected cell lines, MK3 was expressed in the endoplasmic reticulum (ER) membrane, where it bound the cytoplasmic tail of newly synthesized H-2D(b) glycoproteins and targeted them for degradation. Proteasome inhibitors blocked the degradation and led to an accumulation of ubiquitinated H-2D(b). Because this retained its native conformation, ubiquitination preceded any denaturation or dislocation to the cytosol. The PHD/LAP finger of MK3 was not required for H-2D(b) binding but was essential for its ubiquitination and degradation. Thus, gamma -herpesviruses have adapted the cellular PHD/LAP motif to immune evasion, apparently for the catalysis of MHC class I ubiquitination.
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ST BARTHOLOMEWS HOSP, COLL MED, DEPT MED ONCOL, IMPERIAL CANC RES FUND, LONDON EC1M 6BQ, ENGLANDST BARTHOLOMEWS HOSP, COLL MED, DEPT MED ONCOL, IMPERIAL CANC RES FUND, LONDON EC1M 6BQ, ENGLAND
SAHA, V
CHAPLIN, T
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ST BARTHOLOMEWS HOSP, COLL MED, DEPT MED ONCOL, IMPERIAL CANC RES FUND, LONDON EC1M 6BQ, ENGLANDST BARTHOLOMEWS HOSP, COLL MED, DEPT MED ONCOL, IMPERIAL CANC RES FUND, LONDON EC1M 6BQ, ENGLAND
CHAPLIN, T
GREGORINI, A
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ST BARTHOLOMEWS HOSP, COLL MED, DEPT MED ONCOL, IMPERIAL CANC RES FUND, LONDON EC1M 6BQ, ENGLANDST BARTHOLOMEWS HOSP, COLL MED, DEPT MED ONCOL, IMPERIAL CANC RES FUND, LONDON EC1M 6BQ, ENGLAND
GREGORINI, A
AYTON, P
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ST BARTHOLOMEWS HOSP, COLL MED, DEPT MED ONCOL, IMPERIAL CANC RES FUND, LONDON EC1M 6BQ, ENGLANDST BARTHOLOMEWS HOSP, COLL MED, DEPT MED ONCOL, IMPERIAL CANC RES FUND, LONDON EC1M 6BQ, ENGLAND
AYTON, P
YOUNG, BD
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ST BARTHOLOMEWS HOSP, COLL MED, DEPT MED ONCOL, IMPERIAL CANC RES FUND, LONDON EC1M 6BQ, ENGLANDST BARTHOLOMEWS HOSP, COLL MED, DEPT MED ONCOL, IMPERIAL CANC RES FUND, LONDON EC1M 6BQ, ENGLAND
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ST BARTHOLOMEWS HOSP, COLL MED, DEPT MED ONCOL, IMPERIAL CANC RES FUND, LONDON EC1M 6BQ, ENGLANDST BARTHOLOMEWS HOSP, COLL MED, DEPT MED ONCOL, IMPERIAL CANC RES FUND, LONDON EC1M 6BQ, ENGLAND
SAHA, V
CHAPLIN, T
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h-index: 0
机构:
ST BARTHOLOMEWS HOSP, COLL MED, DEPT MED ONCOL, IMPERIAL CANC RES FUND, LONDON EC1M 6BQ, ENGLANDST BARTHOLOMEWS HOSP, COLL MED, DEPT MED ONCOL, IMPERIAL CANC RES FUND, LONDON EC1M 6BQ, ENGLAND
CHAPLIN, T
GREGORINI, A
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h-index: 0
机构:
ST BARTHOLOMEWS HOSP, COLL MED, DEPT MED ONCOL, IMPERIAL CANC RES FUND, LONDON EC1M 6BQ, ENGLANDST BARTHOLOMEWS HOSP, COLL MED, DEPT MED ONCOL, IMPERIAL CANC RES FUND, LONDON EC1M 6BQ, ENGLAND
GREGORINI, A
AYTON, P
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ST BARTHOLOMEWS HOSP, COLL MED, DEPT MED ONCOL, IMPERIAL CANC RES FUND, LONDON EC1M 6BQ, ENGLANDST BARTHOLOMEWS HOSP, COLL MED, DEPT MED ONCOL, IMPERIAL CANC RES FUND, LONDON EC1M 6BQ, ENGLAND
AYTON, P
YOUNG, BD
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h-index: 0
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ST BARTHOLOMEWS HOSP, COLL MED, DEPT MED ONCOL, IMPERIAL CANC RES FUND, LONDON EC1M 6BQ, ENGLANDST BARTHOLOMEWS HOSP, COLL MED, DEPT MED ONCOL, IMPERIAL CANC RES FUND, LONDON EC1M 6BQ, ENGLAND