title: Roles of Chk1 in cell biology and cancer therapy.
abstract: The evolutionally conserved DNA damage response (DDR) and cell cycle checkpoints preserve genome integrity. Central to these genome surveillance pathways is a protein kinase, Chk1. DNA damage induces activation of Chk1, which then transduces the checkpoint signal and facilitates cell cycle arrest and DNA damage repair. Significant progress has been made recently toward our understanding of Chk1 regulation and its implications in cancer etiology and therapy. Specifically, a model that involves both spatiotemporal and conformational changes of proteins has been proposed for Chk1 activation. Further, emerging evidence suggests that Chk1 does not appear to be a tumor suppressor; instead, it promotes tumor growth and may contribute to anticancer therapy resistance. Recent data from our laboratory suggest that activating, but not inhibiting, Chk1 in the absence of chemotherapy might represent an innovative approach to suppress tumor growth. These findings suggest unique regulation of Chk1 in cell biology and cancer etiology, pointing to novel strategies for targeting Chk1 in cancer therapy.
authors.affiliation: Department of Pharmacology, Case Comprehensive Cancer Center, School of Medicine, Case Western Reserve University, Cleveland, OH.
authors.forename: Youwei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Tony
authors.initials: T
authors.lastname: Hunter
mesh_terms: D002453:Cell Cycle; D000071877:Checkpoint Kinase 1; D004261:DNA Replication; D019008:Drug Resistance, Neoplasm; D004789:Enzyme Activation; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D010766:Phosphorylation; D011487:Protein Conformation; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
chemical_list: D011494:Protein Kinases; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1
keywords: Chk1; cancer; cancer therapy; cell cycle checkpoints