Functional studies of the human regulatory protein Ki-1/57 and identification of possible mutations of its gene in cancer

Abstract

The Ki-1/57 protein has been discovered through the cross reactivity of the monoclonal antibody Ki-1 in Hodgkin lymphoma cells. Previous studies described features common to onco-proteins and yeast two-hybrid assays identified protein interaction partners of Ki-1/57 related to transcriptional control and RNA metabolism. Several of Ki-1/57 interacting partners are proteins from the p53 family or that interact with these important transcriptional regulators, known as tumor suppressors and to integrate cell response to stress. CGI-55 it is a possible paralogous protein that shows 40,7 % identity and 67,4 % similarity with Ki-1/57, probably with similar or redundant function. Common protein partners for Ki-1/57 and CGI-55 were described by yeast two-hybrid assays, many of them being nuclear proteins involved in transcriptional control. This suggests a possible nuclear function in the context of transcriptional regulation for Ki-1/57 and CGI-55. Further, Ki-1/57 interacts with splicing proteins, co-localizes with stress granules and is a target of sumoylation. Recent data of microarray assays show further evidence for a possible role in cellular responses to stress, since its overexpression inhibited genes involved in proliferation and cell death. All this data about Ki-1/57, interacting protein partners, microarray and subcellular localization, suggest its action in the gene expression regulation at different levels, from transcription to translation. For more information about Ki-1/57 and CGI-55 function, interference RNA and co-expression of Ki-1/57 and p53 will be done, followed by microarray, cellular and stress studies. Ki-1/57 has been related to cancer, since its higher expression in tumoral cells was observed. In addition to that, the chromosomal locus of the Ki-1/57 gene is in linkage equilibrium in familiar colon cancer. To analyze this relation, the expression of Ki-1/57 in tumor tissues will be investigated by Real-Time PCR and possible mutations in cancer patients will be analyzed by gene sequencing.