Ki-1/57 and CGI-55 ectopic expression impact cellular pathways involved in proliferation and stress response regulation

Show simple item record Vidigal, Pedro M. Costa, Fernanda C. Saito, Ângela Gonçalves, Kaliandra A. Meirelles, Gabriela V. Bressan, Gustavo C. Kobarg, Jörg 2017-11-17T11:10:16Z 2017-11-17T11:10:16Z 2014-09-07
dc.identifier.issn 01674889
dc.description.abstract Ki-1/57 (HABP4) and CGI-55 (SERBP1) are regulatory proteins and paralogs with 40.7% amino acid sequence identity and 67.4% similarity. Functionally, they have been implicated in the regulation of gene expression on both the transcriptional and mRNA metabolism levels. A link with tumorigenesis is suggested, since both paralogs show altered expression levels in tumor cells and the Ki-1/57 gene is found in a region of chromosome 9q that represents a haplotype for familiar colon cancer. However, the target genes regulated by Ki-1/57 and CGI-55 are unknown. Here, we analyzed the alterations of the global transcriptome profile after Ki-1/57 or CGI-55 overexpression in HEK293T cells by DNA microchip technology. We were able to identify 363 or 190 down-regulated and 50 or 27 up-regulated genes for Ki-1/57 and CGI-55, respectively, of which 20 were shared between both proteins. Expression levels of selected genes were confirmed by qRT-PCR both after protein overexpression and siRNA knockdown. The majority of the genes with altered expression were associated to proliferation, apoptosis and cell cycle control processes, prompting us to further explore these contexts experimentally. We observed that overexpression of Ki-1/57 or CGI-55 results in reduced cell proliferation, mainly due to a G1 phase arrest, whereas siRNA knockdown of CGI-55 caused an increase in proliferation. In the case of Ki-1/57 overexpression, we found protection from apoptosis after treatment with the ER-stress inducer thapsigargin. Together, our data give important new insights that may help to explain these proteins putative involvement in tumorigenic events en
dc.format pdf pt-BR
dc.language.iso eng pt-BR
dc.publisher Biochimica et Biophysica Acta (BBA) - Molecular Cell Research pt-BR
dc.relation.ispartofseries 1843: 12, p. 2944-2956, December 2014 pt-BR
dc.rights Open Access pt-BR
dc.subject Ki-1/57 pt-BR
dc.subject CGI-55 pt-BR
dc.subject Microarray pt-BR
dc.subject Gene repressor pt-BR
dc.subject Stress response pt-BR
dc.subject Cell proliferation pt-BR
dc.title Ki-1/57 and CGI-55 ectopic expression impact cellular pathways involved in proliferation and stress response regulation en
dc.type Artigo pt-BR

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    Artigos Técnico-científicos nas áreas de Bioquímica e Biologia Molecular

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