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Active cyclin I-Cdk5 and p35-Cdk5 are both required for podocyte survival. Cyclin I-Cdk5 leads to phosphorylation of MEK1/2 and ERK1/2, which leads to increased levels of the prosurvival proteins Bcl-2 and Bcl-xL. In contrast, p35-Cdk5 increases Bcl-2 protein levels and has no effect on Bcl-xL. Both cyclin I and p35 play pivotal coordinated roles in maintaining podocyte survival during disease.
