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Elevation of UBR2 in muscle of tumor-bearing or free mice caused loss of MHC-IIb and MHC-IIx but not MHC-I and MHC-IIa or other myofibrillar proteins, including \u03b1-actin, troponin, tropomyosin, and tropomodulin. Muscle-specific knockout of UBR2 spared KPC tumor-bearing mice from losing MHC-IIb and MHC-IIx, fast-twitching muscle mass, cross-sectional area, and contractile force. The rectus abdominis (RA) muscle of patients with cachexia-prone cancers displayed a selective reduction of MHC-IIx in correlation with higher UBR2 levels. These data suggest that UBR2 is a regulator of MHC-IIb\/IIx essential for cancer-induced muscle wasting, and that therapeutic interventions can be designed by blocking UBR2 up-regulation by cancer.<\/jats:p>","DOI":"10.1073\/pnas.2200215119","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T15:10:57Z","timestamp":1666019457000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":35,"title":["UBR2 targets myosin heavy chain IIb and IIx for degradation: Molecular mechanism essential for cancer-induced muscle wasting"],"prefix":"10.1073","volume":"119","author":[{"given":"Song","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Integrative Biology and Pharmacology, University of Texas Health Science Center at Houston, Houston, TX 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