Division of Nephrology, University of Washington, Seattle, WA, USA.
Cell Cycle. 2010 May;9(9):1729-31. doi: 10.4161/cc.9.9.11471. Epub 2010 May 10.
Cdk5 has long been recognized to play an important role in development, maturation and apoptosis of postmitotic and terminally differentiated cells. Activation of Cdk5 is tightly regulated by specific activators. Cyclin I was recently characterized as the first cyclin protein that binds to and activates Cdk5. Cyclin I-Cdk5 activates the MEK-ERK pathway and results in increased Bcl-2 and Bcl-X(L) mRNA and protein levels. Lack of Cyclin I renders podocytes more susceptible to apoptosis. Interestingly, activation of Cdk5 by p35 is also involved in the podocytes' response to injury. In the absence of p35, podocytes are more prone to undergo apoptosis. Here, we propose a new model where Cdk5 plays a central role in the cellular response machinery against injury-induced apoptosis of post-mitotic cells. While Cyclin I-Cdk5 regulates Bcl-2 family proteins through activation of the MEK-ERK pathway, p35-Cdk5 directly phosphorylates and stabilizes Bcl-2.
Cdk5 长期以来被认为在有丝分裂后和终末分化细胞的发育、成熟和凋亡中发挥重要作用。Cdk5 的激活受到特定激活剂的严格调节。最近，细胞周期蛋白 I 被描述为第一个与 Cdk5 结合并激活 Cdk5 的 cyclin 蛋白。细胞周期蛋白 I-Cdk5 激活 MEK-ERK 途径，导致 Bcl-2 和 Bcl-X(L)mRNA 和蛋白水平增加。缺乏细胞周期蛋白 I 使足细胞更容易凋亡。有趣的是，p35 激活的 Cdk5 也参与了足细胞对损伤的反应。在没有 p35 的情况下，足细胞更容易发生凋亡。在这里，我们提出了一个新的模型，其中 Cdk5 在针对有丝分裂后细胞损伤诱导凋亡的细胞反应机制中发挥核心作用。虽然细胞周期蛋白 I-Cdk5 通过激活 MEK-ERK 途径调节 Bcl-2 家族蛋白，但 p35-Cdk5 直接磷酸化并稳定 Bcl-2。
