Therapeutic targeting of the E3 ubiquitin ligase SKP2 in T-ALL.

ABSTRACT: Timed degradation of the cyclin-dependent kinase inhibitor p27^Kip1 by the E3 ubiquitin ligase F-box protein SKP2 is critical for T-cell progression into cell cycle, coordinating proliferation and differentiation processes. SKP2 expression is regulated by mitogenic stimuli and by Notch signaling, a key pathway in T-cell development and in T-cell acute lymphoblastic leukemia (T-ALL); however, it is not known whether SKP2 plays a role in the development of T-ALL. Here, we determined that SKP2 function is relevant for T-ALL leukemogenesis, whereas is dispensable for T-cell development. Targeted inhibition of SKP2 by genetic deletion or pharmacological blockade markedly inhibited proliferation of human T-ALL cells in vitro and antagonized disease in vivo in murine and xenograft leuke

SUBMITTER: Rodriguez S 

PROVIDER: S-EPMC7192844 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature