Stabilization of C-terminal binding protein 2 by cellular inhibitor of apoptosis protein 1 via BIR domains without E3 ligase activity
C-terminal binding protein 2 (CtBP2) is a transcriptional co-repressor that regulates many genes involved in normal cellular events. Because CtBP2 overexpression has been implicated in various human cancers, its protein levels must be precisely regulated. Previously, we reported that CtBP1 and CtBP1...
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Veröffentlicht in: | Biochemical and biophysical research communications 2020-09, Vol.530 (2), p.440-447 |
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Zusammenfassung: | C-terminal binding protein 2 (CtBP2) is a transcriptional co-repressor that regulates many genes involved in normal cellular events. Because CtBP2 overexpression has been implicated in various human cancers, its protein levels must be precisely regulated. Previously, we reported that CtBP1 and CtBP1-mediated transcriptional repression are regulated by X-linked inhibitor of apoptosis protein (XIAP). In the present study, we sought to investigate whether CtBP2 is also regulated by XIAP or any other human IAP. We found that cIAP1 interacts with CtBP2 via through BIR domains to regulates the steady-state levels of CtBP2 protein in the nucleus. The levels of CtBP2 were gradually increased upon cIAP1 overexpression and downregulated upon cIAP1 depletion. Interestingly, the RING domain of cIAP1 responsible for E3 ligase activity was not required for this regulation. Finally, the levels of CtBP2 modulated by cIAP1 affected the transcription of CtBP2 target genes and subsequent cell migration. Taken together, our data demonstrate a novel function of cIAP1 which involves protecting CtBP2 from degradation to stabilize its steady-state level. These results suggest that cIAP1 might be a useful target in strategies aiming to downregulate the steady-state level of CtBP2 protein in treating human cancers.
•CtBP2 protein interacts with cIAP1 and cIAP2 in the nucleus.•The levels of CtBP2 protein are modulated by the levels of cIAP1 protein.•Stabilization of CtBP2 protein occurs via interaction with BIR domains of cIAP1 without requirement for RING activity.•Modulation of CtBP2 level by cIAP1 affects the transcription of CtBP2 target genes.•CIAP1 might be a useful target in strategies aiming to downregulate the steady-state level of CtBP2 protein in human cancsers. |
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ISSN: | 0006-291X 1090-2104 |
DOI: | 10.1016/j.bbrc.2020.05.098 |