Journal
PIGMENT CELL & MELANOMA RESEARCH
Volume 26, Issue 2, Pages -Publisher
WILEY-BLACKWELL
DOI: 10.1111/pcmr.12059
Keywords
mahogunin ring finger-1 (MGRN1); pigment-type switching; agouti; melanocortin signaling; TSG101; NEDD4
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Funding
- McLaughlin Research Institute
- National Institute on Aging [R01AG022058]
- American Heart Association
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Mice lacking the E3 ubiquitin ligase mahogunin ring finger-1 (MGRN1) have a pleiotropic phenotype that includes spongiform neurodegeneration, embryonic patterning defects, and dark fur due to a defect in pigment-type switching. The only MGRN1 ubiquitination target identified to date is tumor susceptibility gene 101 (TSG101), a component of the endosomal trafficking machinery. Here, we show that MGRN1 also interacts with but does not ubiquitinate NEDD4, a HECT-domain ubiquitin ligase involved in endosomal trafficking. Using transgenesis in mice, we demonstrate that pigment-type switching likely requires MGRN1s ubiquitin ligase activity but not its ability to bind TSG101 or NEDD4. This indicates that MGRN1-dependent ubiquitination of an as-yet unidentified target protein is required for agouti-mediated melanocortin signaling.
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