The impact of PTEN regulation by CK2 on PI3K-dependent signaling and leukemia cell survival

摘要

Constitutive activation of phosphoinositide 3-kinase (PI3K) (EC 2.7.1.153) signaling pathway is highly prevalent in leukemia and supports tumor cell proliferation and viability. The tumor suppressor phosphatase and tensin homologue deleted on chromosome 10 (PTEN) (EC 3.1.3.67), the main negative regulator of PI3K-dependent signaling, is frequently inactivated in human cancer due to different genetic lesions, which ultimately lead to decreased or absent PTEN protein expression and activity. However, PTEN gene inactivation is not very common in leukemia. Because PTEN is haploinsufficient for tumor suppression, mechanisms that affect PTEN activity might be extremely relevant for cancer development. Recent studies have characterized the importance of the ubiquitous serine/threonine protein kinase CK2 (EC 2.7.11.1) in the non-deleting, posttranslational inhibition of PTEN for the maintenance of leukemia cell viability.