scholarly journals DNA BINDING ACTIVITIES OF THE VINCA ALKALOIDS AND PACLITAXEL AS ANTI-MICROTUBULE DRUGS USED IN CANCER THERAPY

2022 ◽  
Vol 23 (1) ◽  
pp. 51-57
Author(s):  
Emine ÖKSÜZOĞLU
Keyword(s):  
Cancer Therapy ◽  
Dna Binding ◽  
Vinca Alkaloids

scholarly journals Rely on Each Other: DNA Binding Cooperativity Shapes p53 Functions in Tumor Suppression and Cancer Therapy

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2422
Author(s):  
Oleg Timofeev ◽  
Thorsten Stiewe
Keyword(s):  
Cancer Therapy ◽  
Dna Binding ◽  
Cell Fate ◽  
Tumor Suppression ◽  
Quaternary Structure ◽  
Three Dimensional ◽  
Structural Basis ◽  
Sequence Specificity ◽  
Cell Fate Decisions ◽  
Cancer Mutations

p53 is a tumor suppressor that is mutated in half of all cancers. The high clinical relevance has made p53 a model transcription factor for delineating general mechanisms of transcriptional regulation. p53 forms tetramers that bind DNA in a highly cooperative manner. The DNA binding cooperativity of p53 has been studied by structural and molecular biologists as well as clinical oncologists. These experiments have revealed the structural basis for cooperative DNA binding and its impact on sequence specificity and target gene spectrum. Cooperativity was found to be critical for the control of p53-mediated cell fate decisions and tumor suppression. Importantly, an estimated number of 34,000 cancer patients per year world-wide have mutations of the amino acids mediating cooperativity, and knock-in mouse models have confirmed such mutations to be tumorigenic. While p53 cancer mutations are classically subdivided into “contact” and “structural” mutations, “cooperativity” mutations form a mechanistically distinct third class that affect the quaternary structure but leave DNA contacting residues and the three-dimensional folding of the DNA-binding domain intact. In this review we discuss the concept of DNA binding cooperativity and highlight the unique nature of cooperativity mutations and their clinical implications for cancer therapy.

scholarly journals Targeting DNA binding proteins for cancer therapy

2020 ◽  
Vol 111 (4) ◽  
pp. 1058-1064
Author(s):  
Yoshitomo Shiroma ◽  
Ryou‐u Takahashi ◽  
Yuki Yamamoto ◽  
Hidetoshi Tahara
Keyword(s):  
Cancer Therapy ◽  
Dna Binding ◽  
Binding Proteins ◽  
Dna Binding Proteins

scholarly journals Beyond the Paclitaxel and Vinca Alkaloids: Next Generation of Plant-Derived Microtubule-Targeting Agents with Potential Anticancer Activity

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1721 ◽  
Author(s):  
Dangquan Zhang ◽  
Arun Kanakkanthara
Keyword(s):  
Natural Products ◽  
Cancer Therapy ◽  
Anticancer Activity ◽  
Anticancer Agents ◽  
Vinca Alkaloids ◽  
Next Generation ◽  
Stages Of Development ◽  
Microtubule Targeting Agents ◽  
Plant Sources

Plants are an important source of chemically diverse natural products that target microtubules, one of the most successful targets in cancer therapy. Colchicine, paclitaxel, and vinca alkaloids are the earliest plant-derived microtubule-targeting agents (MTAs), and paclitaxel and vinca alkaloids are currently important drugs used in the treatment of cancer. Several additional plant-derived compounds that act on microtubules with improved anticancer activity are at varying stages of development. Here, we move beyond the well-discussed paclitaxel and vinca alkaloids to present other promising plant-derived MTAs with potential for development as anticancer agents. Various biological and biochemical aspects are discussed. We hope that the review will provide guidance for further exploration and identification of more effective, novel MTAs derived from plant sources.

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