dc.contributor.author | Inuzuka, Hiroyuki | |
dc.contributor.author | Fukushima, Hidefumi | |
dc.contributor.author | Shaik, Shavali | |
dc.contributor.author | Liu, Pengda | |
dc.contributor.author | Lau, Alan W. | |
dc.contributor.author | Wei, Wenyi | |
dc.date.accessioned | 2013-02-11T21:54:26Z | |
dc.date.issued | 2011 | |
dc.identifier.citation | Inuzuka, Hiroyuki, Hidefumi Fukushima, Shavali Shaik, Pengda Liu, Alan W. Lau, and Wenyi Wei. 2011. Mcl-1 ubiquitination and destruction. Oncotarget 2(3): 239-244. | en_US |
dc.identifier.issn | 1949-2553 | en_US |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:10288518 | |
dc.description.abstract | Loss of the Fbw7 tumor suppressor is common in diverse human cancer types, including T-Cell Acute Lymphoblastic Leukemia (T-ALL), although the mechanistic basis of its anti-oncogenic activity remains largely unclear. We recently reported that SCF\(^{Fbw7}\) regulates cellular apoptosis by controlling the ubiquitination and destruction of the pro-survival protein, Mcl-1, in a GSK3 phosphorylation-dependent manner. We found that human T-ALL cell lines displayed a close relationship between Fbw7 loss and Mcl-1 overexpression. More interestingly, T-ALL cell lines that are deficient in Fbw7 are particularly sensitive to sorafenib, a multi-kinase inhibitor that has been demonstrated to reduce Mcl-1 expression through an unknown mechanism. On the other hand, Fbw7-deficient T-ALL cell lines are much more resistant to the Bcl-2 antagonist, ABT-737. Furthermore, reconstitution of Fbw7 or depletion of Mcl-1 in Fbw7-deficient cells restores ABT-737 sensitivity, suggesting that elevated Mcl-1 expression is important for Fbw7-deficient cells to evade apoptosis. Therefore, our work provides a novel molecular mechanism for the tumor suppression function of Fbw7. Furthermore, it provides the rationale for targeted usage of Mcl-1 antagonists to treat Fbw7-deficient T-ALL patients. | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | Impact Journals LLC | en_US |
dc.relation.hasversion | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3260810/pdf/ | en_US |
dash.license | LAA | |
dc.title | Mcl-1 Ubiquitination and Destruction | en_US |
dc.type | Journal Article | en_US |
dc.description.version | Version of Record | en_US |
dc.relation.journal | Oncotarget | en_US |
dash.depositing.author | Inuzuka, Hiroyuki | |
dc.date.available | 2013-02-11T21:54:26Z | |
dc.identifier.doi | 10.18632/oncotarget.242 | |
dash.contributor.affiliated | Wei, Wenyi | |
dash.contributor.affiliated | Liu, Pengda | |
dash.contributor.affiliated | Shaik, Shavali | |
dash.contributor.affiliated | Inuzuka, Hiroyuki | |