Abstract

UNC-45A (Protein unc-45 homolog A) is a cytoskeletal-associated protein with a dual and non-mutually exclusive role as a regulator of the actomyosin system and a Microtubule (MT)-destabilizing protein, which is overexpressed in human cancers including in ovarian cancer patients resistant to the MT-stabilizing drug paclitaxel. Mapping of UNC-45A in the mouse upper genital tract and central nervous system reveals its enrichment not only in highly proliferating and prone to remodeling cells, but also in microtubule-rich areas, of the ovaries and the nervous system, respectively. In both apparatuses, UNC-45A is also abundantly expressed in the ciliated epithelium. As regulators of actomyosin contractility and MT stability are essential for the physiopathology of the female reproductive tract and of neuronal development, our findings suggest that UNC-45A may have a role in ovarian cancer initiation and development as well as in neurodegeneration.

Highlights

  • UNC-45A (Protein unc-45 homolog A) is a member of the UCS (UNC-45/CRO1/She4p) protein family [1,2], with dual and non-mutually exclusive roles as a regulator of the actomyosin system [3,4] and a microtubule (MT)-destabilizing protein [5,6,7]

  • We found that UNC-45A is abundantly expressed in cells of the early follicles (Figure 1B, i), the corpus luteum (Figure 1B, ii), and the later follicles (Figure 1B, iii)

  • When we took into into account possible variabilities in the expression of UNC-45A following the hormonal account possible variabilities in the expression of UNC-45A following the hormonal and and structural changes that accompany the progression of the estrous cycle, we found no structural changes that accompany the progression of the estrous cycle, we found no sigsignificant differences in UNC-45A expression pattern in diestrus vs. proestrus

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Summary

Introduction

UNC-45A (Protein unc-45 homolog A) is a member of the UCS (UNC-45/CRO1/She4p) protein family [1,2], with dual and non-mutually exclusive roles as a regulator of the actomyosin system [3,4] and a microtubule (MT)-destabilizing protein [5,6,7]. Regulators of actomyosin contractility and MT stability are essential for both ovarian cancer cell proliferation and neuronal development. MT-destabilizing proteins are expressed in both neurons [14,15,16,17,18] and cancer cells, including ovarian cancer cells [19,20,21], where they play roles spanning from regulating symmetrical and asymmetrical cell division [22] to regulating MT mass [6] and sensitivity to MT-targeting agents [6,23]. UNC-45A is overexpressed in breast and ovarian cancer as compared to their normal counterpart [24,25,26] and in ovarian cancer patients that are resistant to the MT-stabilizing drug paclitaxel [6]

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