TULA: An SH3- And UBA-containing protein that binds to c-Cbl and ubiquitin

Elena A. Feshchenko, Evgeniya V. Smirnova, Gayathri Swaminathan, Anjali M. Teckchandani, Rachana Agrawal, Hamid Band, Xiaolong Zhang, Roland S. Annan, Steven A. Carr, Alexander Y. Tsygankov

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

Bownregulation of protein tyrosine kinases is a major function of the multidomain protein c-Cbl. This effect of c-Cbl is critical for both negative regulation of normal physiological stimuli and suppression of cellular transformation. In spite of the apparent importance of these effects of c-Cbl, their own regulation is poorly understood. To search for possible novel regulators of c-Cbl, we purified a number of c-Cbl-associated proteins by affinity chromatography and identified them by mass spectrometry. Among them, we identified the UBA- and SH3-containing protein T-cell Ubiquitin LigAnd (TULA), which can also bind to ubiquitin. Functional studies in a model system based on co-expression of TULA, c-Cbl, and EGF receptor in 293T cells demonstrate that TULA is capable of inhibiting c-Cbl-mediated downregulation of EGF receptor. Furthermore, modulation of TULA concentration in Jurkat T-lymphoblastoid cells demonstrates that TULA upregulates the activity of both Zap kinase and NF-AT transcription factor. Therefore, our study indicates that TULA counters the inhibitory effect of c-Cbl on protein tyrosine kinases and, thus, may be involved in the regulation of biological effects of c-Cbl. Finally, our results suggest that TULA-mediated inhibition of the effects of c-Cbl on protein tyrosine kinases is caused by TULA-induced ubiquitylation and degradation of c-Cbl.

Original languageEnglish (US)
Pages (from-to)4690-4706
Number of pages17
JournalOncogene
Volume23
Issue number27
DOIs
StatePublished - Jun 10 2004

Keywords

  • Protein tyrosine kinase
  • SH3
  • TULA
  • UBA
  • Ubiquitin
  • c-Cbl

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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  • Cite this

    Feshchenko, E. A., Smirnova, E. V., Swaminathan, G., Teckchandani, A. M., Agrawal, R., Band, H., Zhang, X., Annan, R. S., Carr, S. A., & Tsygankov, A. Y. (2004). TULA: An SH3- And UBA-containing protein that binds to c-Cbl and ubiquitin. Oncogene, 23(27), 4690-4706. https://doi.org/10.1038/sj.onc.1207627