UCS Proteins: Chaperones for Myosin and Co-Chaperones for Hsp90 - The Networking of Chaperones by Co-chaperones - page 145

'spots' that form the actomyosin ring assembly in interphase S. pombe cells (Wong
et al. 2002 ). Maintenance of the myosin-containing spots however, is independent
of F-actin. While the actomyosin ring has a rapid turnover, the interphase spot does
not, showing that this progenitor structure in the interphase is necessary to ensure
proper assembly of the actomyosin ring and successful cell division. Recombinant
full-length Rng3p or its UCS domain alone are necessary and sufficient to activate
the actin-based motility of myosin in vitro and double its actin-activated Mg 2+ -ATP
activity (Lord and Pollard 2004 ; Lord et al. 2008 ). Although Rng3p is specifically
necessary to maintain the activity of intrinsically unstable Myo2, it may possess the
capability of responding to changes in the stability of other myosins (Stark et al.
2013 ). Rng3p was also found to associate with polysomes and bind to mRNAs en-
coding all types of myosin heavy chains, which suggest that Rng3p may be involved
in myosin folding cotranslationally (Amorim and Mata 2009 ).Whether Rng3p and
other fungal UCS proteins require Hsp90 for their myosin-dependent functions is
uncertain. However, in vivo , Swo1p (Hsp90 homolog in S. pombe ) and Rng3p have
been shown to be both required for Myo2 assembly in the contractile ring (Mishra
et al. 2005 ). These observations suggest that some functional relationship exists
between the S. pombe UCS protein and Hsp90.
The CRO1 protein of the filamentous fungus, P. anserina , is a 702-residue pro-
tein that is required for sexual sporulation (Berteaux-Lecellier et al. 1998 ). GFP-
tagging of the CRO1 protein reveals that it is a cytosolic protein expressed mainly
at the beginning of the dikaryotic stage and at the time of ascospore maturation.
The primary defect of null mutant allele of the gene, cro1-1 is the inability to form
septa between the daughter nuclei after mitotic division. The mutant also results in
abortive meiosis of resultant polyploidy nuclei and lack of progression from the
syncytial (vegetative) state to the cellular (sexual) state (Berteaux-Lecellier et al.
1998 ). Unlike the wild type fungal filaments, disorganization of the actin prevents
microtubule disassembly.
UNC-45 and Cancers
Recently, more and more results have been emerging to link UNC-45 to different
cancers. The possible non-myosin function of UNC-45 was first described in pro-
gesterone receptor (PR) chaperoning pathway (Chadli et al. 2006 ). UNC-45A was
identified as a new factor to regulate Hsp90-dependent PR chaperoning in a yeast
two-hybrid screen for additional PR binding factors (Chadli et al. 2006 ). UNC-45A
can interact with PRs in vivo and in vitro . It was shown that UNC-45A inhibits the
activation of Hsp90 by the cochaperone Aha1 and blocks progression of PR chap-
eroning to its hormone binding state in the simplified cell-free system, which limit
Hsp90-dependent PR chaperoning (Chadli et al. 2006 ). Since PR has been impli-
cated in breast cancer for a long time, and not only tumor cell proliferation but also
tumor metastasis depend on myosin's function, researchers began to explore the
relationship between cancer and UNC-45. Ovarian cancer was discovered to have