FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2954838324> ?p ?o ?g. }

• W2954838324 abstract "Mitotic destruction of cyclin A has remained enigmatic ever since it was discovered. Regulation of cyclin A proteolysis appears to be different from that of other mitotic cyclins in diverse species. Despite being substrates of the same destruction machinery - the E3 ligase called Anaphase Promoting Complex/Cyclosome (APC/C) - the proteolysis of cyclin A concludes before that of the B-type cyclins and other crucial substrates like securin. Moreover cyclin B and securin, but not cyclin A, gets stabilized upon activation of the spindle assembly checkpoint, which is a surveillance mechanism that inhibits the APC/C. Somehow, APC/C activity towards cyclin A escapes checkpoint control. Defining the cyclin A destruction signals is paramount for solving this riddle. Unfortunately, in spite of years of research, the cyclin A degradation signal remains ill-defined and poorly characterized. A single and simple destruction box (D-box) motif is responsible for cyclin B turnover. But the cyclin A degradation signal is much more complex. In Drosophila cyclin A (CycA), a putative D-box and another element called the KEN box have been implicated; but eliminating these do not cause stability. In order to characterize the elusive CycA destruction signals, an extensive analysis was carried out in this study. It was found that both the N- and C-terminal regions are involved in turnover, which implies a synergistic action by multiple parts of the molecule. A KEN box, a D-box and an aspartic acid at position 70 are required at the N-terminus and they make additive contributions to degradation when the checkpoint is active or inactive. From the C-terminal region, the cyclin box contributes. Single point mutations in these four elements totally abolish mitotic destruction. Very importantly, it was observed that the cyclin box mediates the spindle checkpoint bypass. The normal function of the cyclin box is to mediate Cdk1 binding, and previous studies had claimed that this interaction is essential for timely destruction. But it was found here that the cyclin box provides a function different from Cdk1 binding for turnover; most likely it presents an interaction motif for the APC/C. Furthermore, eight potential ubiquitin acceptor lysine residues surrounding the N-terminal signals were found to be preferentially used for proteolysis. Combining mutations in these lysines and the N-terminal signals caused full stability leading to mitotic arrest phenotypes. But, mutating the lysines alone only prolonged the duration of mitosis. Thus, presumably, lysines elsewhere on the protein are used when the preferred ones are absent. This apparent shift in ubiquitination is mediated by the N-terminal signals. In conclusion, this study defines the CycA destruction signals and gives an explanation for how checkpoint destruction can be accomplished." @default.
• W2954838324 created "2019-07-12" @default.
• W2954838324 creator A5090967586 @default.
• W2954838324 date "2007-01-01" @default.
• W2954838324 modified "2023-09-27" @default.
• W2954838324 title "Defining the residues governing the mitotic destruction of Drosophila cyclin A" @default.
• W2954838324 cites W1971233013 @default.
• W2954838324 cites W2033141310 @default.
• W2954838324 cites W2049353837 @default.
• W2954838324 hasPublicationYear "2007" @default.
• W2954838324 type Work @default.
• W2954838324 sameAs 2954838324 @default.
• W2954838324 citedByCount "1" @default.
• W2954838324 countsByYear W29548383242014 @default.
• W2954838324 crossrefType "dissertation" @default.
• W2954838324 hasAuthorship W2954838324A5090967586 @default.
• W2954838324 hasConcept C105696609 @default.
• W2954838324 hasConcept C107888121 @default.
• W2954838324 hasConcept C11882975 @default.
• W2954838324 hasConcept C120089663 @default.
• W2954838324 hasConcept C120504264 @default.
• W2954838324 hasConcept C1491633281 @default.
• W2954838324 hasConcept C16438837 @default.
• W2954838324 hasConcept C175732170 @default.
• W2954838324 hasConcept C185592680 @default.
• W2954838324 hasConcept C2778437423 @default.
• W2954838324 hasConcept C2781125876 @default.
• W2954838324 hasConcept C28179978 @default.
• W2954838324 hasConcept C29537977 @default.
• W2954838324 hasConcept C47432576 @default.
• W2954838324 hasConcept C53420372 @default.
• W2954838324 hasConcept C54086632 @default.
• W2954838324 hasConcept C55493867 @default.
• W2954838324 hasConcept C63378162 @default.
• W2954838324 hasConcept C85813293 @default.
• W2954838324 hasConcept C86803240 @default.
• W2954838324 hasConcept C93304396 @default.
• W2954838324 hasConcept C94561458 @default.
• W2954838324 hasConcept C95444343 @default.
• W2954838324 hasConcept C9743823 @default.
• W2954838324 hasConceptScore W2954838324C105696609 @default.
• W2954838324 hasConceptScore W2954838324C107888121 @default.
• W2954838324 hasConceptScore W2954838324C11882975 @default.
• W2954838324 hasConceptScore W2954838324C120089663 @default.
• W2954838324 hasConceptScore W2954838324C120504264 @default.
• W2954838324 hasConceptScore W2954838324C1491633281 @default.
• W2954838324 hasConceptScore W2954838324C16438837 @default.
• W2954838324 hasConceptScore W2954838324C175732170 @default.
• W2954838324 hasConceptScore W2954838324C185592680 @default.
• W2954838324 hasConceptScore W2954838324C2778437423 @default.
• W2954838324 hasConceptScore W2954838324C2781125876 @default.
• W2954838324 hasConceptScore W2954838324C28179978 @default.
• W2954838324 hasConceptScore W2954838324C29537977 @default.
• W2954838324 hasConceptScore W2954838324C47432576 @default.
• W2954838324 hasConceptScore W2954838324C53420372 @default.
• W2954838324 hasConceptScore W2954838324C54086632 @default.
• W2954838324 hasConceptScore W2954838324C55493867 @default.
• W2954838324 hasConceptScore W2954838324C63378162 @default.
• W2954838324 hasConceptScore W2954838324C85813293 @default.
• W2954838324 hasConceptScore W2954838324C86803240 @default.
• W2954838324 hasConceptScore W2954838324C93304396 @default.
• W2954838324 hasConceptScore W2954838324C94561458 @default.
• W2954838324 hasConceptScore W2954838324C95444343 @default.
• W2954838324 hasConceptScore W2954838324C9743823 @default.
• W2954838324 hasLocation W29548383241 @default.
• W2954838324 hasOpenAccess W2954838324 @default.
• W2954838324 hasPrimaryLocation W29548383241 @default.
• W2954838324 hasRelatedWork W1521832405 @default.
• W2954838324 hasRelatedWork W1959249887 @default.
• W2954838324 hasRelatedWork W1967425351 @default.
• W2954838324 hasRelatedWork W1976449876 @default.
• W2954838324 hasRelatedWork W2013680732 @default.
• W2954838324 hasRelatedWork W2019127386 @default.
• W2954838324 hasRelatedWork W2047960762 @default.
• W2954838324 hasRelatedWork W2066331228 @default.
• W2954838324 hasRelatedWork W2075125140 @default.
• W2954838324 hasRelatedWork W2094783227 @default.
• W2954838324 hasRelatedWork W2099011152 @default.
• W2954838324 hasRelatedWork W2189541748 @default.
• W2954838324 hasRelatedWork W2326503995 @default.
• W2954838324 hasRelatedWork W2582223125 @default.
• W2954838324 hasRelatedWork W2591507150 @default.
• W2954838324 hasRelatedWork W2739897759 @default.
• W2954838324 hasRelatedWork W2892351595 @default.
• W2954838324 hasRelatedWork W2981224563 @default.
• W2954838324 hasRelatedWork W3099912599 @default.
• W2954838324 hasRelatedWork W2060534634 @default.
• W2954838324 isParatext "false" @default.
• W2954838324 isRetracted "false" @default.
• W2954838324 magId "2954838324" @default.
• W2954838324 workType "dissertation" @default.