Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P62988 (Ubiquitin)
 4,326 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 26S proteasome is responsible for the degradation of polyubiquitinated proteins. During this process the polyubiquitin chain is removed. The identity of the proteasomal component that is responsible for this activity has not been clear, as it contains no subunits that resemble known deubiquitinating enzymes. The Jab1/MPN domain is a widespread 120 amino acid protein module found in archaea, bacteria, and eukaryotes. In eukaryotes the Jab1/MPN domain is found in subunits of several multiprotein complexes including the proteasome. Recently it has been proposed that the Jab1/MPN domain of the proteasomal subunit Rpn11 is responsible for the removal of the polyubiquitin chain from substrate proteins. Here we report the crystal structure and characterization of AF2198, a Jab1/MPN domain protein from Archaeoglobolus fulgidus. The structure reveals a fold that resembles that of cytidine deaminase and places the Jab1/MPN domain in a superfamily of metal dependent hydrolases.
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PMID:Structure of the Jab1/MPN domain and its implications for proteasome function. 1451 97

Although the covalent attachment of a polyubiquitin is the prevailing paradigm for entry into proteasomes, accumulating evidence suggests that poorly defined ubiquitin-free pathways also degrade proteins. The cytidine deaminase APOBEC3G (A3G) potently inhibits human immunodeficiency virus type 1 replication by disrupting viral reverse transcription. However, human immunodeficiency virus type 1 produces a viral infectivity factor (Vif) to destroy this antiretroviral protein. It was shown that Vif binds to both A3G and a Cullin 5 ubiquitin-protein isopeptide ligase. It is currently accepted that this enzyme polyubiquitylates A3G on lysine residues, resulting in its degradation by proteasomes. Here, we find that A3G without ubiquitylation is still degraded by proteasomes in a Vif-dependent manner. We further show that Vif is polyubiquitylated and that this event could be critical for A3G proteasomal degradation. Thus, A3G is degraded by a novel pathway that might involve ubiquitylation of one protein and then targets a second binding partner for proteasomal entry and degradation. We propose that instead of triggering A3G polyubiquitylation, polyubiquitylated Vif might serve as a vehicle to transport A3G into proteasomes for degradation.
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PMID:APOBEC3G is degraded by the proteasomal pathway in a Vif-dependent manner without being polyubiquitylated. 1832 44