The Abnormal, Mislocalized HR BMH Protein Associates with Members of the Protein Processing Machinery in the Cytoplasm

The study investigated a mutation at the mouse hairless locus, resulting in the hairless rhino bald Mill Hill (Hr rhbmh) phenotype, which produced a larger mutant HR bmh protein due to a 296 bp deletion. This mutant protein, expressed during hair follicle development, was found to interact with the vitamin D receptor (VDR) but failed to repress VDR-mediated transactivation. The HR bmh protein exhibited abnormal cellular localization in both transfected cell lines and the skin of mutant mice. It specifically co-localized and interacted with HDAC6 in the cytoplasm, sharing high sequence homologies. The study explored the implications of HR bmh mis-localization in endosomal processing and proteasome pathways, contributing to the distinct skin phenotype observed in these hairless mutants.