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

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.

Name thesis:degree_name

Cell Biology (Doctoral)

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Cell Biology

Grantor

The University of Texas Medical Branch at Galveston

Author dc:creator

• Guo, Wei

Advisor dc:contributor.advisor

• Boehning, Darren F

Committee members dc:contributor.committeemember

• Epstein, Henry F
• Barral, José M
• May, Gregory S
• Tang, Shao-Jun

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

Handle dc:identifier.uri

http://hdl.handle.net/2152.3/800

OAI identifier oai:identifier

oai:utmb-ir.tdl.org:2152.3/800