Historical Background
Cbl protein (for Casitas B-lineage lymphoma) was discovered as the cellular form of v-Cbl, a retroviral oncoprotein. v-Cbl is a 357 amino acid-long, gag-fusion transforming protein of Cas NS-1 retrovirus, which causes pre- and pro-B lymphomas in mice (Langdon et al. 1989). The cellular Cbl has a length of 906 or 913 amino acids in humans and mice, respectively, so v-Cbl corresponds to a large C-terminal truncation of Cbl (Blake et al. 1991). Following this finding, other Cbl-family members were identified and the role of Cbl-family proteins as key players in cellular regulation was established. The history of research in this area has been outlined in multiple review articles, for example, Tsygankov et al. (2001) and Swaminathan and Tsygankov (2006), etc. During the first years following the discovery of c-Cbl, the prevalent view was that it functions as an adaptor protein. The discovery of the E3 ubiquitin-protein ligase activity of...
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References
Blake TJ, Shapiro M, Morse 3rd HC, Langdon WY. The sequences of the human and mouse c-cbl proto-oncogenes show v-cbl was generated by a large truncation encompassing a proline-rich domain and a leucine zipper-like motif. Oncogene. 1991;6:653–7.
Chitalia V, Shivanna S, Martorell J, Meyer R, Edelman E, Rahimi N. c-Cbl, a ubiquitin E3 ligase that targets active beta-catenin: a novel layer of Wnt signaling regulation. J Biol Chem. 2013;288:23505–17. https://doi.org/10.1074/jbc.M113.473801.
Dangelmaier CA, Quinter PG, Jin J, Tsygankov AY, Kunapuli SP, Daniel JL. Rapid ubiquitination of Syk following GPVI activation in platelets. Blood. 2005;105:3918–24.
Kales SC, Ryan PE, Nau MM, Lipkowitz S. Cbl and human myeloid neoplasms: the Cbl oncogene comes of age. Cancer Res. 2010;70:4789–94. https://doi.org/10.1158/0008-5472.CAN-10-0610.
Katzav S, Schmitz ML. Mutations of c-Cbl in myeloid malignancies. Oncotarget. 2015;6:10689–96. https://doi.org/10.18632/oncotarget.3986.
Langdon WY, Hartley JW, Klinken SP, Ruscetti SK, Morse 3rd HC. v-cbl, an oncogene from a dual-recombinant murine retrovirus that induces early B-lineage lymphomas. Proc Natl Acad Sci U S A. 1989;86:1168–72.
Lee H, Tsygankov AY. Cbl-family proteins as regulators of cytoskeleton-dependent phenomena. J Cell Physiol. 2013;228:2285–93. https://doi.org/10.1002/jcp.24412.
Li M, Kales SC, Ma K, Shoemaker BA, Crespo-Barreto J, Cangelosi AL, et al. Balancing protein stability and activity in cancer: a new approach for identifying driver mutations affecting CBL ubiquitin ligase activation. Cancer Res. 2016;76:561–71. https://doi.org/10.1158/0008-5472.CAN-14-3812.
Matalon O, Fried S, Ben-Shmuel A, Pauker MH, Joseph N, Keizer D, et al. Dephosphorylation of the adaptor LAT and phospholipase C-gamma by SHP-1 inhibits natural killer cell cytotoxicity. Sci Signal. 2016;9:54. https://doi.org/10.1126/scisignal.aad6182.
Mohapatra B, Ahmad G, Nadeau S, Zutshi N, An W, Scheffe S, et al. Protein tyrosine kinase regulation by ubiquitination: critical roles of Cbl-family ubiquitin ligases. Biochim Biophys Acta. 2013;1833:122–39. https://doi.org/10.1016/j.bbamcr.2012.10.010.
Nau MM, Lipkowitz S. Welcome to the family: Cbl-family gene organization, overview of structure and functions of Cbl-related proteins in various taxonomical groups. In: Tsygankov AY, editor. Cbl Proteins. NY: Nova Science Publishers; 2008. p. 3–25.
Oved S, Mosesson Y, Zwang Y, Santonico E, Shtiegman K, Marmor MD, et al. Conjugation to Nedd8 instigates ubiquitylation and down-regulation of activated receptor tyrosine kinases. J Biol Chem. 2006;281:21640–51. https://doi.org/10.1074/jbc.M513034200.
Reddi AL, Duan L, Rainey MA, Ortega-Cava C, Clubb R, Chung BM, et al. Cbl-family E3 ubiquitin ligases as regulators of non-receptor tyrosine kinases. In: Tsygankov A, editor. Cbl proteins. New York: Nova Science Publishers; 2008. p. 53–74.
Rubin C, Yarden Y. CBL-family ubiquitin ligases: negative regulators of receptor tyrosine kinases. In: Tsygankov A, editor. Cbl proteins. New York: Nova Science Publishers; 2008.
Swaminathan G, Tsygankov AY. The Cbl family proteins: ring leaders in regulation of cell signaling. J Cell Physiol. 2006;209:21–43.
Thien CB, Langdon WY. c-Cbl and Cbl-b ubiquitin ligases: substrate diversity and the negative regulation of signalling responses. Biochem J. 2005;391:153–66.
Thomas DH, Getz TM, Newman TN, Dangelmaier CA, Carpino N, Kunapuli SP, et al. A novel histidine tyrosine phosphatase, TULA-2, associates with Syk and negatively regulates GPVI signaling in platelets. Blood. 2010;116:2570–8.
Tsygankov AY. Cbl-family proteins as molecular adaptors. In: Tsygankov A, editor. Cbl proteins. New York: Nova Science Publishers; 2008. p. 75–98.
Tsygankov AY, Teckchandani AM, Feshchenko EA, Swaminathan G. Beyond the RING: CBL proteins as multivalent adapters. Oncogene. 2001;20:6382–402.
Zuo W, Huang F, Chiang YJ, Li M, Du J, Ding Y, et al. c-Cbl-mediated neddylation antagonizes ubiquitination and degradation of the TGF-beta type II receptor. Mol Cell. 2013;49:499–510. https://doi.org/10.1016/j.molcel.2012.12.002.
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Tsygankov, A.Y. (2018). Cbl. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_101564
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DOI: https://doi.org/10.1007/978-3-319-67199-4_101564
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