ABSTRACT
The 57 kDa antigen recognized by the Ki-1 antibody, is also known as intracellular hyaluronic acid binding protein 4 and shares 40.7% identity and 67.4% similarity with serpin mRNA binding protein 1, which is also named CGI-55, or plasminogen activator inhibitor type-1-RNA binding protein-1, indicating that they might be paralog proteins, possibly with similar or redundant functions in human cells. Through the identification of their protein interactomes, both regulatory proteins have been functionally implicated in transcriptional regulation, mRNA metabolism, specifically RNA splicing, the regulation of mRNA stability, especially, in the context of the progesterone hormone response, and the DNA damage response. Both proteins also show a complex pattern of post-translational modifications, involving Ser/Thr phosphorylation, mainly through protein kinase C, arginine methylation and SUMOylation, suggesting that their functions and locations are highly regulated. Furthermore, they show a highly dynamic cellular localization pattern with localizations in both the cytoplasm and nucleus as well as punctuated localizations in both granular cytoplasmic protein bodies, upon stress, and nuclear splicing speckles. Several reports in the literature show altered expressions of both regulatory proteins in a series of cancers as well as mutations in their genes that may contribute to tumorigenesis. This review highlights important aspects of the structure, interactome, post-translational modifications, sub-cellular localization and function of both regulatory proteins and further discusses their possible functions and their potential as tumor markers in different cancer settings.
ABSTRACT
Zinc has been proposed as a promising chemopreventive candidate against colon cancer. However, few studies on the potential beneficial effects of this trace element on cancer chemoprevention are available. The present study was designed to investigate the potential modifying influence of zinc gluconate (ZnGly) on the initiation step of colon carcinogenesis induced by 1,2-dimethylhydrazine (DMH). Male Wistar rats received orally ZnGly (15 mg elemental zinc/kg, 3 times per wk) 2 wk before and during DMH treatment (3 × 40 mg/kg, once a wk). The animals were euthanized at the end of 4th and 16th wk. Colons were analyzed for aberrant crypt foci (ACF) and tumor development. Blood and colon zinc levels, cell proliferation, and apoptosis indexes in colonic crypts were analyzed 24 h after the last DMH administration. Oral treatment with ZnGly did neither alter the number of ACF nor the indexes of cell proliferation and apoptosis in the colonic mucosa. The incidence and multiplicity of colon tumors induced by DMH and their histopathological patterns were not modified by previous treatment with ZnGly. These findings indicate a lack of chemopreventive action of zinc gluconate supplementation on the initiation step of rat colon carcinogenesis induced by DMH.
