SUMO and ubiquitin paths converge

Abstract

One of the more rapidly expanding fields in cell signalling nowadays is the characterization of proteins conjugated to Ub (ubiquitin) or Ub-like peptides, such as SUMO (small Ub-related modifier). The reversible covalent attachment of these small peptides remodels the target protein, providing new protein-protein interaction interfaces, which can be dynamically regulated given a set of enzymes for conjugation and deconjugation. First, ubiquitination was thought to be merely relegated to the control of protein turnover and degradation, whereas the attachment of SUMO was involved in the regulation of protein activity and function. However, the boundaries between the protein fates related to these tag molecules are becoming more and more fuzzy, as either the differences between mono-, multi- and poly-modifications or the lysine residue used for growth of the poly-chains is being dissected. The Ub and SUMO pathways are no longer separated, and many examples of this cross-talk are found in the literature, involving different cellular processes ranging from DNA repair and genome stability, to the regulation of protein subcellular localization or enzyme activity. Here, we review several cases in which SUMOylation and ubiquitination intersect, showing also that the same protein can be conjugated to SUMO and Ub for antagonistic, synergistic or multiple outcomes, illustrating the intricacy of the cellular signalling networks. Ub and SUMO have met and are now applying for new regulatory roles in the cell.

SUMO2/3 is Associated with Ubiquitinated Protein Aggregates in the Mouse Neocortex after Middle Cerebral Artery Occlusion

“…However, over the past decade it has SUMO2/3 coaggregates with ubiquitin after MCAO K Hochrainer et al become clear that in addition to their structural similarities, ubiquitin and SUMO have significant functional interactions. 7,14 These include (1) the competitive targeting of same attachment sites in common substrates, (2) the interdependent conjugation to distinct attachment sites in common targets, or (3) the sequential modification of different targets within the same signaling pathway, leading to antagonistic or synergistic effects on target protein properties. Our data of coprecipitation of SUMO2/3 and ubiquitin from SDS-denatured contents of the aggregate fraction strongly suggest a covalent, direct interaction between the two modifications.…”

GABARAPL1 (GEC1): Original or copycat?

“…Numerous recent studies have focused on elucidating the molecular mechanism of this process and it is now known that the elongation of the phagophore is regulated by two conjugation systems. 61 The first system involves the conjugation of Atg12 to Atg5 by the Atg7 and Atg10 enzymes. The second involves the conjugation of the LC3 protein onto phosphatidylethanolamine by the Atg7 and Atg3 enzymes (reviewed in ref.…”

A Novel Proteomics Approach to Identify SUMOylated Proteins and Their Modification Sites in Human Cells

“…transcription factors, co-activators, and repressors) as well as oncogenes and tumor suppressor genes such as promyelocytic leukemia (PML), murine double minute-2 (Mdm2), c-Myb, c-Jun, and p53 whose misregulation leads to tumorigenesis and metastasis (20). There is growing evidences of cross-talk between protein SUMOylation and ubiquitylation processes (21,22). Earlier reports indicated that SUMOylation can antagonize the ubiquitylation of nuclear factor B (23), whereas recent data also suggest that SUMOylation can be a prerequisite for ubiquitylation and subsequent proteasome-dependent degradation.…”