C-CBL E3 ubiquitin ligase is overexpressed in cutaneous T-cell lymphoma: its inhibition promotes activation-induced cell death.

ABSTRACT: Mycosis fungoides and Sézary syndrome are two major forms of cutaneous T-cell lymphoma (CTCL) characterized by resistance to apoptosis. A central pathway for T-cell apoptosis is activation-induced cell death, which is triggered through the T-cell receptor (TCR). This results in upregulation of FAS ligand (FASL) and subsequent apoptosis through the FAS death receptor pathway. It has been known for more than a decade that TCR signaling is defective in CTCL; however, the underlying mechanism has not been apparent. In this report, we show that the E3 ubiquitin ligase, c-CBL, is overexpressed in CTCL and that its knockdown overcomes defective TCR signaling, resulting in phosphorylation of PLC-g1, calcium influx, ROS generation, upregulation of FASL, and extrinsic pathway apoptosis in CTCL cells

SUBMITTER: Wu J 

PROVIDER: S-EPMC4324119 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature