SUMO and ubiquitin paths converge.
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.
Denuc
Amanda
A
Departament de Genètica, Facultat de Biologia, Universitat de Barcelona, Avda. Diagonal, 645, 08028 Barcelona, Spain.
Marfany
Gemma
G
D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction / Q000502:physiology*; D025841:Small Ubiquitin-Related Modifier Proteins / Q000737:chemistry / Q000378:metabolism*; D025801:Ubiquitin / Q000737:chemistry / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; D025801:Ubiquitin; C120157:TOPORS protein, human; D044767:Ubiquitin-Protein Ligases