| http://purl.uniprot.org/citations/18784078 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18784078 | http://www.w3.org/2000/01/rdf-schema#comment | "We have previously shown that caspase-mediated cleavage of Cyclin E generates p18-Cyclin E in hematopoietic tumor cells. Its expression can induce apoptosis or sensitize to apoptotic stimuli in many cell types. However, p18-cyclin E has a much shorter half-life than Cyclin E, being more effectively ubiquitinated and degraded by the 26 S proteasome. A two-step process has emerged that regulates accelerated degradation of Cyclin E, with a caspase-mediated cleavage followed by enhanced proteasome-mediated degradation. We show that recognition of p18-Cyclin E by the Skp1-Cul1-Fbw7 (SCF) complex and its interaction with the Fbw7 protein isoforms can take place independently of phosphorylation of p18-Cyclin E at a C-terminal phosphodegron. In addition to the SCF(Fbw7) pathway, Ku70 binding that facilitates Hdm2 recruitment may also be implicated in p18-Cyclin E ubiquitination. Blocking p18-Cyclin E degradation with proteasome inhibitors increases levels of p18-Cyclin E and enhances its association with Ku70, thus leading to Bax release, its activation, and apoptosis. Moreover, cells expressing p18-Cyclin E are more sensitive to treatment with proteasome inhibitors, such as Bortezomib. By preventing its proteasomal degradation, p18-Cyclin E, but not Cyclin E, may become an effective therapeutic target for Bortezomib and apoptotic effectors in hematopoietic malignancies."xsd:string |
| http://purl.uniprot.org/citations/18784078 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m804642200"xsd:string |
| http://purl.uniprot.org/citations/18784078 | http://purl.uniprot.org/core/author | "Mazumder S."xsd:string |
| http://purl.uniprot.org/citations/18784078 | http://purl.uniprot.org/core/author | "Matsuyama S."xsd:string |
| http://purl.uniprot.org/citations/18784078 | http://purl.uniprot.org/core/author | "Almasan A."xsd:string |
| http://purl.uniprot.org/citations/18784078 | http://purl.uniprot.org/core/author | "Plesca D."xsd:string |
| http://purl.uniprot.org/citations/18784078 | http://purl.uniprot.org/core/author | "Gama V."xsd:string |
| http://purl.uniprot.org/citations/18784078 | http://purl.uniprot.org/core/date | "2008"xsd:gYear |
| http://purl.uniprot.org/citations/18784078 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/18784078 | http://purl.uniprot.org/core/pages | "30796-30803"xsd:string |
| http://purl.uniprot.org/citations/18784078 | http://purl.uniprot.org/core/title | "A C-terminal fragment of Cyclin E, generated by caspase-mediated cleavage, is degraded in the absence of a recognizable phosphodegron."xsd:string |
| http://purl.uniprot.org/citations/18784078 | http://purl.uniprot.org/core/volume | "283"xsd:string |
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