Studies of the UNC-45A Molecular Chaperone Expression in Human Cancer

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The UCS (UNC-45; Cro-1; She4p) domain proteins are highly evolutionarily conserved proteins, from fungi to mammals, which interact with several types of myosin, involving proper myosin functions. Caenorhabditis elegans UNC-45 acts as a molecular chaperone for myosin. Vertebrate genomes encode two UNC-45 genes: the UNC-45A(a) (general cell isoform) is expressed in many organs, whereas the UNC-45B(b) (striated muscle isoform) is exclusively expressed in striated muscle tissues. Our project reported UNC-45A mRNA and protein expression elevated in human cell lines derived from breast carcinoma metastases. UNC-45A knockdowns decreased breast cancer cells proliferation and invasion rates. We also indicated that UNC-45A(a) existed as two isoforms – UNC-45A(a) 929 and 944 – in mammalian cells. UNC-45A(a) 929 isoform had a long 5' untranslated region (UTR) and 944 isoform had a specific 15 amino acid sequence close to its N-terminus. Furthermore, we showed that UNC-45A 929 accumulated higher level in human breast cells. More importantly, the ubiquitin-proteasome system degraded endogenous UNC-45A and the 15 amino acid sequence unique to UNC-45A 944 protein mediated rapid turnover in mammalian cells.

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UNC-45, myosin, breast cancer, molecular chaperone regulation, protein degradation

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