The nuclear ubiquitin-proteasome system degrades MyoD.
Many short-lived nuclear proteins are targeted for degradation by the ubiquitin-proteasome pathway. The role of the nucleus in regulating the turnover of these proteins is not well defined, although many components of the ubiquitin-proteasome system are localized in the nucleus. We have used nucleoplasm from highly purified HeLa nuclei to examine the degradation of a physiological substrate of the ubiquitin-proteasome system (MyoD). In vitro studies using inhibitors of the system demonstrate MyoD is degraded via the ubiquitin-proteasome pathway in HeLa nucleoplasm. Purified nucleoplasm in vitro also supports the generation of high molecular mass MyoD-ubiquitin adducts. In addition, in vivo studies, using leptomycin B to inhibit nuclear export, demonstrate that MyoD is degraded in HeLa cells by the nuclear ubiquitin-proteasome system.
Floyd
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Edward Mallinckrodt Department of Pediatrics and Molecular Biology and Pharmacology, Washington University School of Medicine, and Division of Pediatric Hematology-Oncology, St. Louis Children's Hospital, St. Louis, Missouri 63110, USA.
Trausch-Azar
J S
JS
Reinstein
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E
Ciechanover
A
A
Schwartz
A L
AL
D000255:Adenosine Triphosphate / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D006868:Hydrolysis; D009097:Multienzyme Complexes / Q000378:metabolism*; D017570:MyoD Protein / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D014452:Ubiquitins / Q000378:metabolism*
D005231:Fatty Acids, Unsaturated; D009097:Multienzyme Complexes; D017570:MyoD Protein; D014452:Ubiquitins; D000255:Adenosine Triphosphate; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C038753:leptomycin B