Ubiquitin system: selectivity and timing of protein destruction.
A growing number of cellular functions have been shown to be regulated through protein degradation. The selective degradation of many short-lived proteins in eukaryotic cells is mediated by the ubiquitin system, by which proteins covalently ligated to ubiquitin are targeted for degradation. The selectivity of the destruction is ensured by the substrate specificity in the ubiquitination steps composed of a series of enzymatic reactions. Ubiquitin-ligase (E3), in conjunction with ubiquitin-conjugating enzyme (E2), has been implicated as playing an essential role in the substrate recognition. The substantial character, however, of the ligase was not clear until several recent studies demonstrated ligases that exert key roles in irreversible steps of the cell-cycle control. In this review, attention is focused on the molecular basis of target recognition of ubiquitination, particularly as exemplified in the ubiquitin-ligases in the cell-cycle control mechanisms.
Yamao
F
F
Laboratory of Mutagenesis, Department of Molecular Genetics, National Institute of Genetics, Mishima, 411-8540, Japan. fyamao@lab. nig.ac.jp
D064173:Anaphase-Promoting Complex-Cyclosome; D002453:Cell Cycle / Q000502:physiology; D005057:Eukaryotic Cells; D006801:Humans; D008025:Ligases / Q000378:metabolism*; D010453:Peptide Synthases / Q000378:metabolism; D044843:SKP Cullin F-Box Protein Ligases; D015398:Signal Transduction; D013997:Time Factors; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases; D014452:Ubiquitins / Q000378:metabolism*