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MLK4 activates the JNK pathway leading to increased expression and stabilization of cell cycle inhibitors p21 and p15 to suppress cellular proliferation. LOF mutations in MLK4, similar to DAPK3, act in a dominant negative manner to suppress activation of WT MLK4. This results in inactivation of the JNK signaling cascade and decreased abundance of p21 and p15 and consequently increased cell proliferation.
