title: Ki-1/57 and CGI-55 ectopic expression impact cellular pathways involved in proliferation and stress response regulation.
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.
authors.affiliation: Laboratório Nacional de Biociências, Centro Nacional de Pesquisa em Energia e Materiais, Campinas, São Paulo, Brasil. Electronic address: fernanda.costa@lnbio.cnpem.br.
authors.forename: Fernanda C
authors.initials: FC
authors.lastname: Costa
authors.affiliation: Laboratório Nacional de Biociências, Centro Nacional de Pesquisa em Energia e Materiais, Campinas, São Paulo, Brasil; Departamento de Bioquímica-Programa de Pós-graduação em Biologia Funcional e Molecular, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, São Paulo, Brasil. Electronic address: angela.saito@lnbio.cnpem.br.
authors.forename: Angela
authors.initials: A
authors.lastname: Saito
authors.affiliation: Laboratório Nacional de Biociências, Centro Nacional de Pesquisa em Energia e Materiais, Campinas, São Paulo, Brasil; Departamento de Bioquímica-Programa de Pós-graduação em Biologia Funcional e Molecular, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, São Paulo, Brasil. Electronic address: kaliandra.goncalves@lnbio.cnpem.br.
authors.forename: Kaliandra A
authors.initials: KA
authors.lastname: Gonçalves
authors.affiliation: Laboratório de Bioinformática, Instituto de Biotecnologia Aplicada à Agropecuária-BIOAGRO, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brasil. Electronic address: pmvidigal@gmail.com.
authors.forename: Pedro M
authors.initials: PM
authors.lastname: Vidigal
authors.affiliation: Laboratório Nacional de Biociências, Centro Nacional de Pesquisa em Energia e Materiais, Campinas, São Paulo, Brasil. Electronic address: gabriela.meirelles@lnbio.cnpem.br.
authors.forename: Gabriela V
authors.initials: GV
authors.lastname: Meirelles
authors.affiliation: Laboratório Nacional de Biociências, Centro Nacional de Pesquisa em Energia e Materiais, Campinas, São Paulo, Brasil; Departamento de Bioquímica-Programa de Pós-graduação em Biologia Funcional e Molecular, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, São Paulo, Brasil. Electronic address: gustavo.bressan@ufv.br.
authors.forename: Gustavo C
authors.initials: GC
authors.lastname: Bressan
authors.affiliation: Laboratório Nacional de Biociências, Centro Nacional de Pesquisa em Energia e Materiais, Campinas, São Paulo, Brasil; Departamento de Bioquímica-Programa de Pós-graduação em Biologia Funcional e Molecular, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, São Paulo, Brasil; Departamento de Genética, Evolução e Bioagentes - Programa de Pós-graduação em Genética e Biologia Molecular, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, São Paulo, Brasil. Electronic address: jorg.kobarg@lnbio.cnpem.br.
authors.forename: Jörg
authors.initials: J
authors.lastname: Kobarg
keywords: CGI-55; Cell proliferation; Gene repressor; Ki-1/57; Microarray; Stress response