In Silico Structural and Functional Characterization of the RSUME Splice Variants

GEREZ, J.A.; FUERTES, M.; TEDESCO, L.; SILBERSTEIN, S.; SEVLEVER, G.; PAEZ-PEREDA, M.; HOLSBOER, F.; TURJANSKI, A.G.; ARZT, E.

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2013 p. 1 - 13

1932-6203

RSUME (RWD-containing SUMO Enhancer) is a small protein that increases SUMO conjugation to proteins. To date, foursplice variants that codify three RSUME isoforms have been described, which differ in their C-terminal end. Comparing thestructure of the RSUME isoforms we found that, in addition to the previously described RWD domain in the N-terminal, allthese RSUME variants also contain an intermediate domain. Only the longest RSUME isoform presents a C-terminal domainthat is absent in the others. Given these differences, we used the shortest and longest RSUME variants for comparativestudies. We found that the C-terminal domain is dispensable for the SUMO-conjugation enhancer properties of RSUME. Wealso demonstrate that these two RSUME variants are equally induced by hypoxia. The NF-kB signaling pathway is inhibitedand the HIF-1 pathway is increased more efficiently by the longest RSUME, by means of a greater physical interaction ofRSUME267 with the target proteins. In addition, the mRNA and protein levels of these isoforms differ in human gliomasamples; while the shortest RSUME isoform is expressed in all the tumors analyzed, the longest variant is expressed in mostbut not all of them. The results presented here show a degree of redundancy of the RSUME variants on the SUMO pathway.However, the increased inhibition conferred by RSUME267 over the NF-kB signaling pathway, the increased activation overthe HIF-1 pathway and the different expression of the RSUME isoforms suggest specific roles for each RSUME isoform whichmay be relevant in certain types of brain tumors that express RSUME, like human pituitary adenomas and gliomas.Authors Fuertes M and Gerez J contributed equally to this work.