RWD domain-containing protein 3

Definition

Enhancer of SUMO conjugation. Via its interaction with UBE2I/UBC9, increases SUMO conjugation to proteins by promoting the binding of E1 and E2 enzymes, thioester linkage between SUMO and UBE2I/UBC9 and transfer of SUMO to specific target proteins which include HIF1A, PIAS, NFKBIA, NR3C1 and TOP1. Isoform 1 and isoform 2 positively regulate the NF-kappa-B signaling pathway by enhancing the sumoylation of NF-kappa-B inhibitor alpha (NFKBIA), promoting its stabilization which consequently leads to an increased inhibition of NF-kappa-B transcriptional activity. Isoform 1 and isoform 2 negatively regulate the hypoxia-inducible factor-1 alpha (HIF1A) signaling pathway by increasing the sumoylation of HIF1A, promoting its stabilization, transcriptional activity and the expression of its target gene VEGFA during hypoxia. Isoform 2 promotes the sumoylation and transcriptional activity of the glucocorticoid receptor NR3C1 and enhances the interaction of SUMO1 and NR3C1 with UBE2I/UBC9. Has no effect on ubiquitination.

References:

[1]. Juan Gerez, et al. In silico structural and functional characterization of the RSUME splice variants. PLoS One. 2013;8(2):e57795. [Content Brief]

[2]. B Shan, et al. RSUME is implicated in HIF-1-induced VEGF-A production in pituitary tumour cells. Endocr Relat Cancer. 2012 Jan 9;19(1):13-27. [Content Brief]

[3]. Jimena Druker, et al. RSUME enhances glucocorticoid receptor SUMOylation and transcriptional activity. Mol Cell Biol. 2013 Jun;33(11):2116-27. [Content Brief]

[4]. Alberto Carbia-Nagashima, et al. RSUME, a small RWD-containing protein, enhances SUMO conjugation and stabilizes HIF-1alpha during hypoxia. Cell. 2007 Oct 19;131(2):309-23. [Content Brief]

生物医学辞典

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