Cdc7 kinase - a new target for drug development.
The cell division cycle 7 (Cdc7) is a serine threonine kinase that is of critical importance in the regulation of normal cell cycle progression. Cdc7 kinase is highly conserved during evolution and much has been learned about its biological roles in humans through the study of lower eukaryotes, particularly yeasts. Two important regulator proteins, Dbf4 and Drf1, bind to and modulate the kinase activity of human Cdc7 which phosphorylates several sites on Mcm2 (minichromosome maintenance protein 2), one of the six subunits of the replicative DNA helicase needed for duplication of the genome. Through regulation of both DNA synthesis and DNA damage response, both key functions in the survival of tumour cells, Cdc7 becomes an attractive target for pharmacological inhibition. There are much data available on the pre-clinical anti-cancer effects of Cdc7 depletion and although there are no available Cdc7 inhibitors in clinical trials as yet, several lead compounds are being optimised for this purpose. In this review, we will address the current status of Cdc7 as an important target for new drug development.
Swords
Ronan
R
Cancer Therapy and Research Center,University of Texas Health Science Center, San Antonio, TX, USA. swordsr@uthscsa.edu
Mahalingam
Devalingam
D
O'Dwyer
Michael
M
Santocanale
Corrado
C
Kelly
Kevin
K
Carew
Jennifer
J
Giles
Francis
F
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D004249:DNA Damage; D004261:DNA Replication; D004273:DNA, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009369:Neoplasms / Q000201:enzymology / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000172:deficiency / Q000502:physiology
D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D004273:DNA, Neoplasm; D047428:Protein Kinase Inhibitors; C068619:CDC7 protein, human; D017346:Protein Serine-Threonine Kinases