Fig. 5

(A) CDK5 signaling in hepatocellular carcinoma. CDK5 mRNA levels are upregulated by lnc-ATG9B-4, leading to aggressive phenotypes. CDK5 interacts with hypoxia-inducing factor-1α (HIF-1α) and phosphorylates it at S687. This stabilizes HIF-1α by preventing its proteasomal degradation and promoting angiogenesis by transcriptionally upregulating VEGFA, VEGFR1 and Ephrin A1. CDK5 also regulates metastasis in HCC by regulating TPX2. CDK5-mediated phosphorylation of TPX2 at S486 increases its stability, leading to tumorigenesis and metastasis. CDK5 activates mTORC1 by phosphorylating PRMT1 at S307, which results in its cytoplasmic translocation. Active PRMT1 in turn methylates WDR24, a critical component of the GATOR2 complex. This results in the inhibition of GATOR1, which in turn activates mTOR signaling, leading to tumorigenesis. (B) CDK5 promotes pituitary adenoma: CDK5 increases VEGF expression in pituitary adenoma. CDK5 also associates with VEGFR2 and phosphorylates it at S229, which is required for normal cell surface expression of VEGFR2 and for inducing cell migration and invasion