CDK5:CABLES:ABL CABLES Cables link CDK5 and ABL1 Authored: Ouwehand, WH, 2010-11-12 CDK5 and ABL1 enzyme substrate 1 (Cables1) is a negative regulator of cell proliferation. Loss of Cables1 function can lead to uncontrolled growth in vivo, observed in many human cancers, such as colon, lung and gynecological malignancies including ovarian and endometrial cancers (Sakamoto et al. 2008). Cables1 is up-regulated by progesterone and down-regulated by estrogen (Zukerberg et al. 2004). Cables1 is predominantly located in the nucleus of proliferating cells (Zukerberg et al. 2000, Wu et al. 2001) but some fully differentiated cells such as mature neurons have a significant proportion in the cytoplasm. Cables1 interacts with cyclin-dependent kinases (Cdk) 2, 3 and 5 (Wu et al. 2001, Matsuoka et al. 2000, Zukerberg et al. 2000). In neurons, Cables1 links Cdk5 and c-Abl, enhancing Cdk5 tyrosine-15 phosphorylation which results in increased Cdk5 activity, important in neurite outgrowth (Zukerberg et al. 2000). In proliferating cells, Cables1 links Cdk2 and Wee1, a dual specificity kinase. Phosphorylation of Cdk2 on tyrosine-15 by Wee-1 leads to decreased Cdk2 activity, Cables1 enhances this inhibitory phosphorylation (Wu et al. 2001). Cables1 has also been shown to interact with two regulators of apoptosis, p53 and p73. The physiological relevance of this interaction is not fully understood, but Cables1 augments p53-induced apoptosis in human osteosarcoma cells (Tsuji et al. 2002). Cables2 interacts with Cdk3, Cdk5 and c-Abl (Sato et al. 2002). Edited: Jupe, S, 2010-11-12 Pubmed10873625 Pubmed10896159 Pubmed11585773 Pubmed11706030 Pubmed11955625 Pubmed14729625 Pubmed18059193 Reactome Database ID Release 431013833 Reactome, http://www.reactome.org ReactomeREACT_25197 Reviewed: Akkerman, JW, 2010-10-29