Chemistry and biology of the ubiquitin signal.
Ubiquitination is one of the most utilized posttranslational modifications in eukaryotes and is involved in a wide range of cellular processes, but is mostly known as a signal for proteasomal degradation. Recently, it has become clear that the ubiquitin signal is far more complex and is dictated by the ubiquitin component and the substrate. The remarkable diversity of the ubiquitin signaling process has triggered an incredible amount of effort to investigate the role of ubiquitination on biological processes. However, despite more than three decades of studies, several important questions remain unanswered. A major hurdle is the inability to obtain homogeneous ubiquitin bioconjugates in sufficient amounts from cells or by application of the enzymatic machinery. Recent breakthroughs in chemical and semisynthetic strategies, however, offer solutions to these challenges. In this Review, we survey the fundamental biological aspects of the ubiquitin signal and present the emerging non-enzymatic approaches for overcoming these obstacles.
Department of Chemistry, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Liat
L
Spasser
Ashraf
A
Brik
D000818:Animals; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction; D025801:Ubiquitin / Q000378:metabolism*; D054875:Ubiquitination
D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex