Ubiquitin-dependent Destruction of Topoisomerase I Is Stimulated by the Antitumor Drug Camptothecin
TLDR
It is demonstrated that independent of DNA replication, the TOP1 cleavable complex is ubiquitinated and destroyed in cells treated with antitumor drugs that block the religation step of the Topoisomerase I reaction.About:
This article is published in Journal of Biological Chemistry.The article was published on 1997-09-26 and is currently open access. It has received 253 citations till now. The article focuses on the topics: Camptothecin & Topoisomerase.read more
Citations
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Development of the Proteasome Inhibitor Velcade™ (Bortezomib)
Julian Adams,Michael Kauffman +1 more
TL;DR: A novel pharmacodynamic assay has shown that bortezomib–mediated proteasome blockade is dose-dependent and reversible, and phase II trials have been initiated for both solid and hematological malignancies.
Journal ArticleDOI
Dynamic proteomics of individual cancer cells in response to a drug.
Ariel Cohen,Naama Geva-Zatorsky,Eran Eden,Milana Frenkel-Morgenstern,Irina Issaeva,Alex Sigal,Ron Milo,Cellina Cohen-Saidon,Yuvalal Liron,Zvi Kam,Lydia Cohen,Tamar Danon,Natalie Perzov,Uri Alon +13 more
TL;DR: A dynamic-proteomics approach is presented that measures the levels and locations of nearly 1000 different endogenously tagged proteins in individual living cells at high temporal resolution, and identifies proteins whose dynamics differ widely between cells, in a way that corresponds to the outcomes—cell death or survival.
Journal Article
Enhanced Chemosensitivity to CPT-11 with Proteasome Inhibitor PS-341: Implications for Systemic Nuclear Factor-κB Inhibition
James C. Cusack,Rong Liu,Michael Houston,Karin Abendroth,Peter J. Elliott,Julian Adams,Albert S. Baldwin +6 more
TL;DR: Proteasome inhibition blocks chemotherapy-induced NF-kappaB activation, leading to a dramatic augmentation of chemosensitivity and enhanced apoptosis, which has significant potential to overcome the high incidence of chemotherapy resistance.
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Mechanism of action of eukaryotic dna topoisomerase i and drugs targeted to the enzyme
TL;DR: The present review describes the topoisomerase I catalytic mechanisms with particular emphasis on the cleavage complex that represents the enzyme's catalytic intermediate and the site of action for camptothecins.
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All tangled up: how cells direct, manage and exploit topoisomerase function
TL;DR: It is shown that topoisomerase activity is indispensible to cells, but requires the transient breakage of DNA strands, which has been exploited, often for significant clinical benefit, by various exogenous agents that interfere with cell proliferation.
References
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Book
Molecular Cloning: A Laboratory Manual
TL;DR: Molecular Cloning has served as the foundation of technical expertise in labs worldwide for 30 years as mentioned in this paper and has been so popular, or so influential, that no other manual has been more widely used and influential.
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Camptothecin induces protein-linked DNA breaks via mammalian DNA topoisomerase I.
TL;DR: It is proposed that camptothecin blocks the rejoining step of the breakage-reunion reaction of mammalian DNA topoisomerase I, which results in the accumulation of a cleavable complex which resembles the transient intermediate proposed for eukaryotic DNATopoisomersase I.
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The ubiquitin-proteasome proteolytic pathway
TL;DR: Two studies clearly demonstrate that the ubiquitin-proteasome system is involved not only in complete destruction of its protein substrates, but also in limited proteolysis and posttranslational processing in which biologically active peptides or fragments are generated.
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Inhibition of Proteasome Activities and Subunit-Specific Amino-Terminal Threonine Modification by Lactacystin
Gabriel Fenteany,Robert F. Standaert,William S. Lane,Soongyu Choi,E. J. Corey,Stuart L. Schreiber +5 more
TL;DR: Lactacystin appears to modify covalently the highly conserved amino-terminal threonine of the mammalian proteasome subunit X (also called MB1), a close homolog of the LMP7 proteasom subunit encoded by the major histocompatibility complex and may have a catalytic role.
Journal Article
Arrest of Replication Forks by Drug-stabilized Topoisomerase I-DNA Cleavable Complexes as a Mechanism of Cell Killing by Camptothecin
TL;DR: It is proposed that the collision between moving replication forks and camptothecin-stabilized topoisomerase I-DNA cleavable complexes results in fork arrest and possibly fork breakage, which are lethal to proliferating cells.