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Human Regulatory Protein Ki-1/57 Is a Target of SUMOylation and Affects PML Nuclear Body Formation

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Saito, Angela ; Souza, Edmarcia E. ; Costa, Fernanda C. ; Meirelles, Gabriela V. ; Goncalves, Kaliandra A. ; Santos, Marcos T. ; Bressan, Gustavo C. ; McComb, Mark E. ; Costello, Catherine E. ; Whelan, Stephen A. ; Kobarg, Jorg
Número total de Autores: 11
Tipo de documento: Artigo Científico
Fonte: JOURNAL OF PROTEOME RESEARCH; v. 16, n. 9, p. 3147-3157, SEP 2017.
Citações Web of Science: 1

Ki-1/57 is a nuclear and cytoplasmic regulatory protein first identified in malignant cells from Hodgkin's lymphoma. It is involved in gene expression regulation on both transcriptional and mRNA metabolism levels. Ki-1/57 belongs to the family of intrinsically unstructured proteins and undergoes phosphorylation by PKC and methylation by PRMT1. Previous characterization of its protein interaction profile by yeast two-hybrid screening showed that Ki-1/57 interacts with proteins of the SUMOylation machinery, the SUMO E2 conjugating enzyme UBC9 and the SUMO E3 ligase PIAS3, which suggested that Ki-1/57 could be involved with this process. Here we identified seven potential SUMO target sites (lysine residues) on Ki-1/57 sequence and observed that Ki-1/57 is modified by SUMO proteins in vitro and in vivo. We showed that SUMOylation of Ki-1/57 occurred on lysines 213, 276, and 336. In transfected cells expressing FLAG-Ki-1/57 wild-type, its paralog FLAG-CGI-55 wild-type, or their non-SUMOylated triple mutants, the number of PML-nuclear bodies (PML-NBs) is reduced compared with the control cells not expressing the constructs. More interestingly, after treating cells with arsenic trioxide (As2O3), the number of PML-NBs is no longer reduced when the non-SUMOylated triple mutant Ki-1/57 is expressed, suggesting that the SUMOylation of Ki-1/57 has a role in the control of As2O3-induced PML-NB formation. A proteome-wide analysis of Ki-1/57 partners in the presence of either SUMO-1 or SUMO-2 suggests that the involvement of Ki-1/57 with the regulation of gene expression is independent of the presence of either SUMO-1 or SUMO-2; however, the presence of SUMO-1 strongly influences the interaction of Ki-1/57 with proteins associated with cellular metabolism, maintenance, and cell cycle. (AU)

Processo FAPESP: 08/57906-3 - Instituto Nacional de Fotônica Aplicada à Biologia Celular - INFABIC
Beneficiário:Hernandes Faustino de Carvalho
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 14/21700-3 - Caracterização funcional de camundongos e células nocaute para os genes que codificam as proteínas regulatórias Ki-1/57 e CGI-55
Beneficiário:Jörg Kobarg
Linha de fomento: Auxílio à Pesquisa - Regular