Barata João T
Instituto de Medicina Molecular, Faculdade de Medicina, Unversidade de Lisboa, Lisboa, Portugal.
Adv Enzyme Regul. 2011;51(1):37-49. doi: 10.1016/j.advenzreg.2010.09.012. Epub 2010 Oct 28.
Gene alterations affecting elements of PI3K signaling pathway do not appear to be sufficient to explain the extremely high frequency of PI3K signaling hyperactivation in leukemia. It has been known for long that PTEN phosphorylation at the C-terminal tail, in particular by CK2, contributes to the stabilization and simultaneous inhibition of this critical tumor suppressor. However, direct evidence of the involvement of this mechanism in cancer has been gathered only recently. It is now known that CK2-mediated posttranslational, non-deleting, inactivation of PTEN occurs in T-ALL, CLL and probably other leukemias and solid tumors. To explore this knowledge for therapeutic purposes remains one of the challenges ahead.
影响PI3K信号通路元件的基因改变似乎不足以解释白血病中PI3K信号过度激活的极高频率。长期以来已知，PTEN在C末端尾巴的磷酸化，特别是由CK2介导的磷酸化，有助于这种关键肿瘤抑制因子的稳定和同时抑制。然而，直到最近才收集到该机制参与癌症的直接证据。现在已知CK2介导的PTEN的翻译后、非缺失性失活发生在T-ALL、CLL以及可能的其他白血病和实体瘤中。为了治疗目的探索这一知识仍然是未来的挑战之一。
