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1. Dynamics and Molecular Mechanisms of p53 Transcriptional Activation

Author:
Offutt, Tavina L.; Ieong, Pek U.; Demir, Özlem; Amaro, Rommie E.
Source:
Biochemistry 2018 v.57 no.46 pp. 6528-6537
ISSN:
1520-4995
Subject:
DNA; DNA damage; DNA-binding domains; apoptosis; asymmetry; cell cycle checkpoints; crystal structure; drug resistance; genome; genomics; humans; hypoxia; models; molecular dynamics; mutants; neoplasms; site-directed mutagenesis; transcription factors; transcriptional activation
Abstract:
... The “guardian of the genome”, p53, functions as a tumor suppressor that responds to cell stressors such as DNA damage, hypoxia, and tumor formation by inducing cell-cycle arrest, senescence, or apoptosis. Mutation of p53 disrupts its tumor suppressor function, leading to various types of human cancers. One particular mutant, R175H, is a structural mutant that inactivates the DNA damage response pa ...
DOI:
10.1021/acs.biochem.8b01005

2. Reduction of Cisplatin-Induced Ototoxicity without Compromising Its Antitumor Activity

Author:
Surnar, Bapurao; Kolishetti, Nagesh; Basu, Uttara; Ahmad, Anis; Goka, Erik; Marples, Brian; Kolb, David; Lippman, Marc E.; Dhar, Shanta
Source:
Biochemistry 2018 v.57 no.46 pp. 6500-6513
ISSN:
1520-4995
Subject:
DNA; DNA damage; adverse effects; antineoplastic activity; aspirin; cisplatin; drug therapy; in vitro studies; models; nausea; nephrotoxicity; neurotoxicity; patients; urinary bladder neoplasms
Abstract:
... Cisplatin is a major chemotherapeutic that continues to have a significant impact in the treatment of more than 50% of all cancers. Since its Food and Drug Administration approval in 1978 for the treatment of advanced ovarian and bladder cancer, this chemotherapeutic has made significant strides and its application has been extended to a large variety of other cancers. However, the vast majority o ...
DOI:
10.1021/acs.biochem.8b00712