Abstract
CKIP-1 is an activator of the Smurf1 ubiquitin ligase acting to promote the ubiquitylation of Smad5 and MEKK2. The mechanisms involved in the recognition and degradation of these substrates by the proteasome remain unclear. Here, we show that CKIP-1, through its leucine zipper, interacts directly with the Rpt6 ATPase of the 19S regulatory particle of the proteasome. CKIP-1 mediates the Smurf1-Rpt6 interaction and delivers the ubiquitylated substrates to the proteasome. Depletion of CKIP-1 reduces the degradation of Smurf1 and its substrates by Rpt6. These findings reveal an unexpected adaptor role of CKIP-1 in coupling the ubiquitin ligase and the proteasome.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATPases Associated with Diverse Cellular Activities
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism*
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Carrier Proteins / chemistry
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Carrier Proteins / metabolism*
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HEK293 Cells
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Humans
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Intracellular Signaling Peptides and Proteins
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LIM Domain Proteins / genetics
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LIM Domain Proteins / metabolism*
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Proteasome Endopeptidase Complex / metabolism*
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Protein Binding
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Protein Interaction Domains and Motifs
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Protein Subunits / metabolism*
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Proteolysis*
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RNA, Small Interfering
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Ubiquitin-Protein Ligases / metabolism*
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Ubiquitination
Substances
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Adaptor Proteins, Signal Transducing
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Carrier Proteins
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Intracellular Signaling Peptides and Proteins
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LIM Domain Proteins
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PLEKHO1 protein, human
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PSMC5 protein, human
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Protein Subunits
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RNA, Small Interfering
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Transcription Factors
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SMURF1 protein, human
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Ubiquitin-Protein Ligases
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Proteasome Endopeptidase Complex
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ATPases Associated with Diverse Cellular Activities