Functional identity of receptors for proteolysis-inducing factor on human and murine skeletal muscle


Background: Cachexia in both mice and humans is associated with tumour production of a sulphated glycoprotein called proteolysis-inducing factor (PIF). In mice PIF binds with high affinity to a surface receptor in skeletal muscle, but little is known about the human receptor. This study compares the human PIF receptor with the murine. Methods: Human PIF was isolated from the G361 melanoma and murine PIF from the MAC16 colon adenocarcinoma. The human PIF receptor was isolated from human skeletal muscle myotubes. Protein synthesis and degradation induced by human and murine PIF was studied in human and murine skeletal muscle myotubes. Results: Both the human and murine PIF receptors showed the same immunoreactivity and Mr 40 000. Both murine and human PIF inhibited total protein synthesis and stimulated protein degradation in human and murine myotubes to about the same extent, and this was attenuated by a rabbit polyclonal antibody to the murine PIF receptor, but not by a non-specific rabbit antibody. Both murine and human PIF increased the activity of the ubiquitin-proteasome pathway in both human and murine myotubes, as evidenced by an increased 'chymotrypsin-like' enzyme activity, protein expression of the 20S and 19S proteasome subunits, and increased expression of the ubiquitin ligases MuRF1 and MAFbx, and this was also attenuated by the anti-mouse PIF receptor antibody. Conclusions: These results suggest that the murine and human PIF receptors are identical.

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Divisions: College of Health & Life Sciences > Aston Pharmacy School
College of Health & Life Sciences
College of Health & Life Sciences > Chronic and Communicable Conditions
Additional Information: Author can archive publisher's version/PDF after a 12 months embargo . Creative & © 2014 Cancer Research UK. Commons Attribution Non-Commercial Share Alike License
Uncontrolled Keywords: cancer cachexia,murine and human PIF receptors,protein synthesis and degradation,proteolysis-inducing factor (PIF),skeletal muscle,Cancer Research,Oncology
Publication ISSN: 1532-1827
Last Modified: 16 Feb 2024 08:08
Date Deposited: 02 Jun 2015 14:20
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Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2014-08-26
Authors: Mirza, K.A.
Tisdale, M.J.

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