Szemraj Janusz, Rozpończyk Elzbieta, Bartkowiak Jacek, Greger Janusz, Oszajca Katarzyna
Department of Biochemistry, Institute of Physiology and Biochemistry, Medical University of Lodz, 6/8 Mazowiecka St., 92-215 Lodz, Poland.
Postepy Biochem. 2005;51(1):44-51.
The basis of oncogenesis underlies the modification of the control of the cell cycle, which leads to disturb balance between proliferation and apoptosis. The MDM2 protein suppresses the ability of p53 to activate genes responsible for repairing or apoptosis, but also promotes p53 degradation by ubiquitination. MDM2 inhibits tumor suppressor property of pRb, by releasing E2F1, which stimulates DNA synthesis in S-phase. MDM2 influences on the neuronal and muscle differentiation. Quantity and stability of the MDM2 protein is regulated by p73, p53, TSG101, p14ARF and Ras-Raf-MEK-ERK pathway. Changes of the level of the MDM2 can disturb control of cell cycle and contribute to oncogenesis.
肿瘤发生的基础在于细胞周期调控的改变,这会导致增殖与凋亡之间的平衡失调。MDM2蛋白既能抑制p53激活负责修复或凋亡的基因的能力,还能通过泛素化促进p53降解。MDM2通过释放E2F1抑制pRb的肿瘤抑制特性,E2F1可刺激S期的DNA合成。MDM2影响神经元和肌肉分化。MDM2蛋白的数量和稳定性受p73、p53、TSG101、p14ARF和Ras-Raf-MEK-ERK信号通路调控。MDM2水平的变化会扰乱细胞周期调控并促进肿瘤发生。