Fludarabine nucleoside induces major changes in the p53 interactome in human B-lymphoid cancer cell lines

Autor: Juhura G. Almazi, Munther Alomari, Larissa Belov, O. Giles Best, Yandong Shen, Mark E. Graham, Stephen P. Mulligan, Richard I. Christopherson
Rok vydání: 2021
Předmět:
Zdroj: Nucleosides, nucleotidesnucleic acids. 41(3)
ISSN: 1532-2335
Popis: Triple combination FCR (fludarabine, cyclophosphamide and rituximab) is often used as front-line treatment for chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma. Results from our laboratory indicate that 2-FaraAMP (fludarabine) has multiple mechanisms of cytotoxicity that include accumulation of isoforms and phosphorylated derivatives of p53, and induction of the unfolded protein response (UPR). Using protein pull-downs with Dynabeads coated with p53 antibody, we have found that 2-FaraA (fludarabine nucleoside) induces major changes in the p53 interactome in human Raji lymphoma and IM9 multiple myeloma cells. These changes are likely driven by DNA strand breaks induced by 2-FaraA that activate protein kinases such as ATM, ATR and Chk1.
Databáze: OpenAIRE