| Full text | |
| Author(s): Show less - |
Saito, Angela
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Souza, Edmarcia E.
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Costa, Fernanda C.
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Meirelles, Gabriela V.
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Goncalves, Kaliandra A.
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Santos, Marcos T.
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Bressan, Gustavo C.
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McComb, Mark E.
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Costello, Catherine E.
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Whelan, Stephen A.
;
Kobarg, Jorg
Total Authors: 11
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| Document type: | Journal article |
| Source: | JOURNAL OF PROTEOME RESEARCH; v. 16, n. 9, p. 3147-3157, SEP 2017. |
| Web of Science Citations: | 1 |
| Abstract | |
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) | |
| FAPESP's process: | 14/21700-3 - Functional characterization of mice and their cells in which the genes encoding the regulatory proteins Ki-1/57 and CGI-55 have been knocked out |
| Grantee: | Jörg Kobarg |
| Support Opportunities: | Regular Research Grants |