Academic Commons


Lack of PTEN sequesters CHK1 and initiates genetic instability

Puc, Janusz; Keniry, Megan; Li, Hong Shen; Pandita, Tej K.; Choudhury, Atish D.; Memeo, Lorenzo; Mansukhani, Mahesh M.; Vundavalli, Murty V.; Gaciong, Zbigniew; Meek, Sarah E.M.; Piwnica-Worms, Helen; Hibshoosh, Hanina; Parsons, Ramon E.

Pten−/− cells display a partially defective checkpoint in response to ionizing radiation (IR). The checkpoint defect was traced to the ability of AKT to phosphorylate CHK1 at serine 280, since a nonphosphorylated mutant of CHK1 (S280A) complemented the checkpoint defect and restored CDC25A degradation. CHK1 phosphorylation at serine 280 led to cova- lent binding of 1 to 2 molecules of ubiquitin and cytoplasmic CHK1 localization. Primary breast carcinomas lacking PTEN expression and having elevated AKT phosphorylation had increased cytoplasmic CHK1 and displayed aneuploidy (p < 0.005). We conclude that loss of PTEN and subsequent activation of AKT impair CHK1 through phosphorylation, ubiquitination, and reduced nuclear localization to promote genomic instability in tumor cells.


  • thumnail for Puc J et al Cancer Cell 2005.pdf Puc J et al Cancer Cell 2005.pdf application/pdf 841 KB Download File

Also Published In

More About This Work

Academic Units
Institute for Cancer Genetics
Pathology and Cell Biology
Published Here
November 19, 2019
Academic Commons provides global access to research and scholarship produced at Columbia University, Barnard College, Teachers College, Union Theological Seminary and Jewish Theological Seminary. Academic Commons is managed by the Columbia University Libraries.