PTEN mutations or deletions are repeated in T ALL and PTEN deletions are related to less favorable outcome in T ALL. e PTEN status of the cell affects drug sensitivity. For instance, therapy of T ALL with gamma secretase inhibitor was only efficient when the cells indicated functional PTEN. One mechanism by which Notch confers GC Afatinib solubility resistance is through PTEN inhibition resulting in Akt activation. PTEN specically catalyzes the dephosphorylation of phosphate of the inositol ring in phosphatidylinositol triphosphate resulting in the biphosphate product phosphatidyl biphosphate. PIP3 is really a 2nd messenger generated by PI3K that binds to the pleckstrin homology domain of Akt, which allows its phosphorylation and activation by the 3 phosphoinositide dependent protein kinase 1. Regulation of PTEN Stability by Ubiquitination and Phosphorylation Digestion. Taken into consideration the crucial role of PTEN in identifying drug sensitivity, mechanisms controlling PTEN activity and stability have strong impact on the drug response. PTEN is controlled by several mechanisms. Besides gene mutation and deletion, paid off PTEN phrase is related to epigenetic events such as promoter methylation. In the level, ubiquitination and phosphorylation decrease PTEN protein degrees, while oxidation and acetylation reduce PTEN activity. Rak phosphorylation of PTEN at Tyr336 balances the PTEN protein, while phosphorylation at r366, Ser370, Ser380, r382, and Ser385 by casein kinase 2 and GSK3 decreases its stability. PTEN is controlled by the protooncogene ubiquitin ligase NEDD4 1 that encourages PTEN for proteasomal degradation. In numerous human cancer products where the genetic background of PTEN was normal, Erlotinib solubility but its protein level was low, NEDD4 1 was highly expressed. Upon TCR/CD28 activation of T cells, inactivation is undergone by PTEN by NEDD4 1. Elizabeth connection between PTEN and NEDD4 might be inhibited by the E3 ubiquitin ligase Cbl b. Cblb/ T cells show improved Akt action, that has been abrogated by simultaneous deciency in NEDD4. PTEN can also be negatively regulated by the anti apoptotic XIAP that promotes PTEN for polyubiquitination and proteosomal degradation. Induction of apoptosis in B CLL by arsenic trioxide was demonstrated to result in activation of c Jun NH2 final kinase, inactivation of AKT and PTEN up-regulation, XIAP down-regulation, and NFB. Two other E3 ligases downregulating PTEN CHIP, and include WWP2. Recently, PTEN was shown to be up-regulated by dexamethasone. PTEN term can also be repressed with a range of microRNAs like the miR miR 29b, miR 106b25, miR 21, miR 26a, 1792 group, miR 214, miR 216a and miR 217, miR 212, miR 221, and miR 222.