Fig. 8
From: CDK5: an oncogene or an anti-oncogene: location location location
(A) CDK5 acts as an oncogene in HNSCC. Tyrosine-phosphorylated active STAT3 induces the expression of miR-21, which in turn upregulates CDK5 and p35. CDK5/p35 in turn increase the nuclear translocation of β-catenin, leading to EMT, invasion and metastasis. Green circle shows activating phosphorylation event. (B) CDK5 promotes survival in leukemia cells. BH3-only protein NOXA plays dual roles in proliferating hematopoietic cancer. In the presence of glucose, NOXA is phosphorylated by CDK5 at S13 and is sequestered in a cytosolic complex that imparts a metabolic (growth and survival) advantage. Both glucose deprivation and CDK5 inhibition promote apoptosis by dephosphorylating NOXA. (C) CDK5 acts as a molecular rheostat in neuronal and nonneuronal tissues. Upregulation of CDK5 and p35 in neurons and nonneuronal tissues has distinct consequences. While overexpression of CDK5 and/or p35 in neurons is neuroprotective, it is oncogenic in nonneuronal tissues. Nevertheless, emerging evidence suggests that hyperactivation of CDK5 by p25 formation is toxic in both neurodegenerative diseases and cancer