BBB seminar: Alexander Tsygankov
TULA: A novel regulator of protein ubiquitylation and degradation?
Hovedinnhold
Alexander Tsygankov
Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, PA, USA
The protooncogenic protein c-Cbl functions as an adaptor protein and an E3 ubiquitin-protein ligase. The latter activity is crucial for the negative regulation of protein tyrosine kinases (PTKs) in a variety of cell types; active PTKs become ubiquitylated by c-Cbl, which binds to them, and are degraded as a result. We have recently identified TULA, a lymphoid c-Cbl-binding protein that possesses SH3 and UBA domains, and showed that these domains bind to c-Cbl and ubiquitin, respectively. We have also demonstrated that TULA counteracts c-Cbl-dependent downregulation of PTKs and PTK-mediated signaling in a UBA-dependent fashion. At least in some cases, the inhibition of c-Cbl-dependent downregulation of PTK may be dependent on an increase in the ubiquitylation of c-Cbl in the presence of TULA (1). Taken together, TULA may act as a negative regulator of the downregulatory effects of c-Cbl on PTKs. However, general considerations related to the complexity of TULA's structure and some results from our laboratory, and other laboratories, suggest that TULA is likely to have functions other than the protection of PTKs from c-Cbl-mediated degradation.
1. Feshchenko, E.A., Swaminathan, G., Teckchandani, A. M., Agrawal, R., Smirnova, E. V., Zhang, X., Annan, R. S., Carr, S. A., Tsygankov, A. Y. TULA: An SH3- and UBA-containing protein that binds to c-Cbl and ubiquitin. Oncogene, 2004, 23, 4690-4706.
Host: Aurelia Lewis, Department of Biomedicine
| Prof. Alexander Tsygankov has his PhD from the Bach Institute of Biochemistry in Moscow. He continued his scientific career first in Germany and then in Pennsylvania, USA, where he started his own group at the Dept. of Microbiology and Immunology, Temple University, Philadelphia, 10 years ago. His main research activity focuses on signal transduction mediated by protein tyrosine kinases. The aim is to elucidate the biological role of the multidomain protein c-Cbl, in particular in relation to its effects on cell adhesion, morphology and anchorage-independent growth. These studies are crucial in the understanding of how c-Cbl suppresses cellular transformation and have contributed greatly to the elucidation of the function of the CBL protein family (relevant review: Tsygankov et al. Beyond the RING: CBL proteins as multiple adapters. Oncogene, 2001, 20:6382-6402). Tsygankov's group has discovered TULA, a new protein interacting with c-Cbl and ubiquitin; he will present recent developments in this field. |