SKP2 regulates TERT independently of RUNX1/ETO in AML subtypes lacking the t(8,21) translocation via CDKN1B and RB phosphorylation states.

SKP2 has been shown to be essential for cancer growth as SKP2 ubiquitinates various proteins. This event leads to the degradation of proteins crucial towards cancer development from which malignancy trailed. Here we investigated the role of SKP2 in TERT modulation in non t (8,21) AML. Previously, one of the underlying mechanisms of TERT control in t(8,21) AML was elucidated by our research group whereby RUNX1/ETO regulated TERT levels via stabilization of SKP2. Here, in non t(8,21) AML cell lines, direct suppression of SKP2 also led to TERT suppression and concomitant accumulation of CDKN1B. Moreover, SKP2 suppression led to an increase in levels of underphosphorylated RB while no changes in E2F1 levels were observed. Additionally, inverse correlation was observed between FOXO3 (reduced) and c-Myc (increased) protein levels post SKP2 suppression indicating compensatory MYC activation of TERT. However, no changes in MYC occupation on TERT promoter was observed following SKP2 suppression and TERT remain suppressed thus subjugating the notion of TERT related MYC compensatory mechanisms. Collectively, the results of this study show that SKP2 regulate TERT levels independently of RUNX1/ETO in AML subtypes lacking the t(8;21) translocation directly via CDKN1B and RB phosphorylation states.