Tcl1 interacts with Atm and enhances NF-κB activation in hematologic malignancies

Eugenio Gaudio, Riccardo Spizzo, Francesco Paduano, Zhenghua Luo, Alexey Efanov, Alexey Palamarchuk, Amanda S. Leber, Mohamed Kaou, Nicola Zanesi, Arianna Bottoni, Stefan Costinean, Laura Z. Rassenti, Tatsuya Nakamura, Thomas J. Kipps, Rami I. Aqeilan, Yuri Pekarsky, Francesco Trapasso, Carlo M. Croce

Research output: Contribution to journalArticle

Abstract

The T-cell leukemia/lymphoma 1 (TCL1) oncogene is a target of chromosomal translocations and inversions at 14q31.2, and its rearrangement in T cells causes T-cell prolymphocytic leukemias. TCL1 dysregulation in B cells is responsible for the development of an aggressive form of chronic lymphocytic leukemia (CLL), the most common human leukemia. We have investigated the mechanisms underlying the oncogenic functions of Tcl1 protein using a mass spectrometry approach and have identified Atm (ataxia-telangiectasia mutated) as a candidate Tcl1-interacting protein. The Tcl1-Atm complex formation was validated by coimmunoprecipitation experiments. Importantly, we show that the association of Atm with Tcl1 leads to enhanced IκBα phosphorylation and ubiquitination and subsequent activation of the NF-κB pathway. Our findings reveal functional cross-talk between Atm and Tcl1 and provide evidence for a novel pathway that could be targeted in leukemias and lymphomas.

Original languageEnglish
Pages (from-to)180-187
Number of pages8
JournalBlood
Volume119
Issue number1
DOIs
Publication statusPublished - Jan 5 2012

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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    Gaudio, E., Spizzo, R., Paduano, F., Luo, Z., Efanov, A., Palamarchuk, A., Leber, A. S., Kaou, M., Zanesi, N., Bottoni, A., Costinean, S., Rassenti, L. Z., Nakamura, T., Kipps, T. J., Aqeilan, R. I., Pekarsky, Y., Trapasso, F., & Croce, C. M. (2012). Tcl1 interacts with Atm and enhances NF-κB activation in hematologic malignancies. Blood, 119(1), 180-187. https://doi.org/10.1182/blood-2011-08-374561