Abstract
Background and Objectives: DNA damage activates signaling pathways that arrest the cell cycle to provide time for repairing of lesions and control the activation of these DNA repair processes or to induce the apoptosis program in the case of too severe damage. Defects in these so-called checkpoint pathways can result in genomic instability and mutagenesis which in mammals can lead to cancer. The crucial role of Chk2 in the DNA damage response pathway is evidenced by the findings that Chk2 -/- ES cells were defective in maintaining gamma-IR-induced G2-phase arrest and that Chk2 null thymocytes failed to stabilize p53 and to induce G1-phase arrest and apoptosis. Moreover, heterozygous mutations in the Chk2 gene have been identified in human inherited and sporadic cancers, suggesting that Chk2 acts as a tumor suppressor.
Materials and Methods: In order to discover new regulators of Chk2, we have performed a yeast two- hybrid screen. We used human Chk2 as a bait and also human cDNA library to find out proteins interacting with Chk2. The yeast used in this project was AH109 strain.
Results: We found that Chk2 associated with several different proteins including. Protein phosphatase 2A (PP2A). The association of PP2A was studied further in several experiments and its association has been confirmed.
Conclusion: PP2A is a highly conserved serine/threonine phosphatase that regulates a variety of cellular processes, including signal transduction, control of DNA replication, apoptosis and cell cycle progression. We have found the association of this protein with Chk2. This association indicates that PP2A is involved in controlling cell cycle. Further studies is required to investigate the involvement of this protein in human cancer.