GSK-3 beta inhibition - At the crossroad between Akt and mTOR constitutive activation to enhance cyclin D1 protein stability in mantle cell lymphoma
Jessica Dal Col, Riccardo Dolcetti
CELL CYCLE | TAYLOR & FRANCIS INC | Published : 2008
Strategies able to downregulate the aberrant expression of cyclin D1 may prove of therapeutic relevance in cancer patients. This is particularly true for mantle cell lymphoma (MCL) in which cyclin D1 is overexpressed as a consequence of the t(11;14)(q13;q32) translocation. We have recently demonstrated that an increased cyclin D1 stability also contributes to the high levels of this protein observed in MCL cells. This effect is mediated by a constitutive activation of PI3-K/Akt, which keeps GSK-3beta inhibited. Here we show that inhibition of PI3-K/Akt induces a 40% decrease of cyclin D1 half-life as a result of accumulation of the dephosphorylated/active form of GSK-3beta within the nucleus..View full abstract
This work was supported by grants from the Italian Association for Cancer Research (AIRC) to R. Dolcetti. J. Dal Col is a fellowship recipient of AIRC.