Journal ArticleDOI
Deregulation of the ubiquitin system and p53 proteolysis modify the apoptotic response in B-CLL lymphocytes.
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TLDR
It is shown that only specific—not nonspecific—proteasomal inhibitors can discriminate between malignant and normal lymphocytes in inducing the apoptotic death response, and raises the possibility that two different proteolytic pathways controlling p53 stability may be pathologically imbalanced.About:
This article is published in Blood.The article was published on 2000-07-01. It has received 93 citations till now. The article focuses on the topics: Lactacystin & Programmed cell death.read more
Citations
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Journal ArticleDOI
The proteasome: a suitable antineoplastic target
TL;DR: A proteasome inhibitor — bortezomib — has been developed that has shown efficacy as an anticancer agent in the clinic and how can targeting such a universal, broadly active cellular component provide the selectivity and specificity that are required for cancer therapeutics?
Journal ArticleDOI
The p53-Mdm2 module and the ubiquitin system.
Dan Michael,Moshe Oren +1 more
TL;DR: The p53 tumor suppressor protein is a short-lived protein, which is stabilized in response to cellular stress, and the exact site of degradation of p53 is presently under debate.
Journal ArticleDOI
The development of proteasome inhibitors as anticancer drugs
TL;DR: Efficacy and safety results from a phase 2 clinical trial contributed to approval of bortezomib for use in patients with relapsed and refractory multiple myeloma who have received at least 2 prior therapies and have demonstrated disease progression on their last therapy.
Journal ArticleDOI
Proteasome inhibitors in cancer therapy: lessons from the first decade.
TL;DR: This saga provides a salient example of the promise of translational medicine and a paradigm by which other agents may be successfully brought from the bench to the bedside.
Journal ArticleDOI
The proteasome: a novel target for cancer chemotherapy.
JB Almond,Gerald M. Cohen +1 more
TL;DR: The induction of apoptosis by proteasome inhibitors varies between cell types but often occurs following an initial accumulation of short-lived proteins such as p53, p27, pro-apoptotic Bcl-2 family members or activation of the stress kinase JNK.
References
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Journal ArticleDOI
The Ubiquitin System
Avram Hershko,Aaron Ciechanover +1 more
TL;DR: This review discusses recent information on functions and mechanisms of the ubiquitin system and focuses on what the authors know, and would like to know, about the mode of action of ubi...
Journal ArticleDOI
p53, the Cellular Gatekeeper for Growth and Division
TL;DR: The author regrets the lack of citations for many important observations mentioned in the text, but their omission is made necessary by restrictions in the preparation of review manuscripts.
Journal ArticleDOI
Mdm2 promotes the rapid degradation of p53
TL;DR: It is proposed that the Mdm2-promoted degradation of p53 provides a new mechanism to ensure effective termination of the p53 signal.
Journal ArticleDOI
Regulation of p53 stability by Mdm2
TL;DR: It is shown that interaction with Mdm2 can also result in a large reduction in p53 protein levels through enhanced proteasome-dependent degradation, which may contribute to the maintenance of low p53 concentrations in normal cells.
Journal ArticleDOI
p53 is required for radiation-induced apoptosis in mouse thymocytes
TL;DR: It is demonstrated that immature thymocytes lacking p53 die normally when exposed to compounds that may mimic T-cell receptor engagement and to glucocorticoids but are resistant to the lethal effects of ionizing radiation.
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