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Expanding the ubiquitin code through post‐translational modification
Author(s) -
Herhaus Lina,
Dikic Ivan
Publication year - 2015
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201540891
Subject(s) - ubiquitin , phosphorylation , acetylation , autophagy , parkin , pink1 , microbiology and biotechnology , biology , ubiquitin ligase , ubiquitin protein ligases , mitochondrion , optineurin , sumo protein , biochemistry , chemistry , mitophagy , parkinson's disease , gene , medicine , apoptosis , disease , pathology
Ubiquitylation is among the most prevalent post‐translational modifications ( PTM s) and regulates numerous cellular functions. Interestingly, ubiquitin (Ub) can be itself modified by other PTM s, including acetylation and phosphorylation. Acetylation of Ub on K6 and K48 represses the formation and elongation of Ub chains. Phosphorylation of Ub happens on multiple sites, S57 and S65 being the most frequently modified in yeast and mammalian cells, respectively. In mammals, the PINK 1 kinase activates ubiquitin ligase Parkin by phosphorylating S65 of Ub and of the Parkin Ubl domain, which in turn promotes the amplification of autophagy signals necessary for the removal of damaged mitochondria. Similarly, TBK 1 phosphorylates the autophagy receptors OPTN and p62 to initiate feedback and feedforward programs for Ub‐dependent removal of protein aggregates, mitochondria and pathogens (such as S almonella and M ycobacterium tuberculosis ). The impact of PINK 1‐mediated phosphorylation of Ub and TBK 1‐dependent phosphorylation of autophagy receptors ( OPTN and p62) has been recently linked to the development of Parkinson's disease and amyotrophic lateral sclerosis, respectively. Hence, the post‐translational modification of Ub and its receptors can efficiently expand the Ub code and modulate its functions in health and disease.