Alternative titles; symbols
HGNC Approved Gene Symbol: CABLES1
Cytogenetic location: 18q11.2 Genomic coordinates (GRCh38) : 18:23,134,564-23,260,470 (from NCBI)
CABLES1 is a cyclin-dependent kinase (CDK)-binding protein that plays a role in proliferation and/or differentiation (Zukerberg et al., 2004).
Using Cdk3 (123828) as bait in a yeast 2-hybrid screen of a mouse brain cDNA library, Matsuoka et al. (2000) cloned Cables1, which they designated Ik3-1. The C terminus of the deduced 568-amino acid protein, which Matsuoka et al. (2000) referred to as p70(Ik3-1), shares significant homology with the cyclin boxes of C-type cyclins (123838) and A-type cyclins (see 604036). Northern blot analysis showed a periodicity of Cables1 expression during the cell cycle in a mouse macrophage cell line. Expression was upregulated during G1 progression, maximal at mid-late G1, and declined gradually thereafter.
Wu et al. (2001) cloned full-length human CABLES from a fetal brain cDNA library. Immunohistochemical analysis of human fibroblasts detected endogenous CABLES expressed in a diffuse nuclear pattern. Strong diffuse nuclear staining was also seen in normal squamous and glandular epithelium. In proliferating HeLa and T-lymphoblastic leukemia cells, CABLES was predominantly localized to the nuclear fraction, with only a small amount in the cytoplasmic and membrane fractions.
By mutation analysis, Matsuoka et al. (2000) determined that the cyclin box-like domain of mouse Cables1 is not required for its interaction with Cdk3.
By yeast 2-hybrid analysis of embryonic day-14.5 whole mouse embryos, Zukerberg et al. (2000) found that Cables interacted with kinase-inactive Cdk5 (123831). Cables enhanced tyr15 phosphorylation of Cdk5 by Abl (189980), resulting in increased kinase activity of the p35 (CDK5R1; 603460)/Cdk5 complex in developing neurons. Expression of antisense Cables in primary neurons caused axonal shortening, whereas expression of active Abl caused axonal lengthening. Zukerberg et al. (2000) concluded that Cables and Cdk5 tyrosine phosphorylation are involved in axon growth regulation.
By immunoprecipitation analysis, Wu et al. (2001) found that CABLES associated with a multiprotein complex that included CDK2 (116953), cyclin A, cyclin E (see 123837), and p21 (CDKN1A; 116899) in HeLa cells. CDK2 became tyrosine phosphorylated when CABLES or WEE1 (193525) were overexpressed, and the level of phosphorylation increased exponentially when CABLES and WEE1 were coexpressed. CABLES overexpression inhibited HeLa cell growth, decreased the rate of DNA synthesis, and inhibited colony formation. Wu et al. (2001) concluded that CABLES enhances the inhibitory kinase activity of WEE1, leading to reduced CDK2 kinase activity. Wu et al. (2001) also found loss of CABLES expression in 50 to 60% of primary colon and head and neck cancer samples, which was associated with loss of heterozygosity on chromosome 18q11.
Dong et al. (2003) noted significant loss of CABLES expression in some ovarian cancers, particularly serous and endometrioid carcinomas. However, they found no correlation between loss of CABLES and histologic grade, tumor stage, or survival.
By FISH, Wu et al. (2001) mapped the CABLES gene to chromosome 18q11.2-q12.1.
Zukerberg et al. (2004) found that Cables -/- mice were viable and were born at expected mendelian ratios. Matings between Cables -/- mice revealed reduced female fertility and fecundity compared with wildtype females. The uterine tracts of Cables -/- mice were abnormally large and distended, and mutant females were more susceptible than wildtype mice to estrogen-induced endometrial adenocarcinomas.
Dong, Q., Kirley, S., Rueda, B., Zhao, C., Zukerberg, L., Oliva, E. Loss of Cables, a novel gene on chromosome 18q, in ovarian cancer. Mod. Path. 16: 863-868, 2003. [PubMed: 13679449] [Full Text: https://doi.org/10.1097/01.MP.0000084434.88269.0A]
Matsuoka, M., Matsuura, Y., Semba, K., Nishimoto, I. Molecular cloning of a cyclin-like protein associated with cyclin-dependent kinase 3 (cdk 3) in vivo. Biochem. Biophys. Res. Commun. 273: 442-447, 2000. Note: Erratum: Biochem. Biophys. Res. Commun. 274: 880 only, 2000. [PubMed: 10873625] [Full Text: https://doi.org/10.1006/bbrc.2000.2965]
Wu, C.-L., Kirley, S. D., Xiao, H., Chuang, Y., Chung, D. C., Zukerberg, L. R. Cables enhances Cdk2 tyrosine 15 phosphorylation by Wee1, inhibits cell growth, and is lost in many human colon and squamous cancers. Cancer Res. 61: 7325-7332, 2001. [PubMed: 11585773]
Zukerberg, L. R., DeBernardo, R. L., Kirley, S. D., D'Apuzzo, M., Lynch, M. P., Littell, R. D., Duska, L. R., Boring, L., Rueda, B. R. Loss of Cables, a cyclin-dependent kinase regulatory protein, is associated with the development of endometrial hyperplasia and endometrial cancer. Cancer Res. 64: 202-208, 2004. [PubMed: 14729625] [Full Text: https://doi.org/10.1158/0008-5472.can-03-2833]
Zukerberg, L. R., Patrick, G. N., Nikolic, M., Humbert, S., Wu, C.-L., Lanier, L. M., Gertler, F. B., Vidal, M., Van Etten, R. A., Tsai, L.-H. Cables links Cdk5 and c-Abl and facilitates Cdk5 tyrosine phosphorylation, kinase upregulation, and neurite outgrowth. Neuron 26: 633-646, 2000. [PubMed: 10896159] [Full Text: https://doi.org/10.1016/s0896-6273(00)81200-3]