Tcl1 enhances Akt kinase activity and mediates its nuclear translocation

Yuri Pekarsky, Anatoliy Koval, Cora Hallas, Roberta Bichi, Maria Tresini, Scott Malstrom, Giandomenico Russo, Philip Tsichlis, Carlo M. Croce

Research output: Contribution to journalArticle


The TCL1 oncogene at 14q32.1 is involved in the development of human mature T-cell leukemia. The mechanism of action of Tcl1 is unknown. Because the virus containing the v-akt oncogene causes T-cell lymphoma in mice and Akt is a key player in transduction of antiapoptotic and proliferative signals in T-cells, we investigated whether Akt and TCl1 function in the same pathway. Coimmunoprecipitation experiments showed that endogenous Akt1 and Tcl1 physically interact in the T-cell leukemia cell line SupT11; both proteins also interact when cotransfected into 293 cells. Using several AKT1 constructs in cotransfection experiments, we determined that this interaction occurs through the pleckstrin homology domain of the Akt1 protein. We further demonstrated that, in 293 cells transfected with TCL1, the endogenous Akt1 bound to Tcl1 is 5-10 times more active compared with Akt1 not bound to Tcl1. The intracellular localization of Tcl1 and Akt1 in mouse fibroblasts was investigated by immunofluorescence. When transfected alone, Akt1 was found only in cytoplasm whereas Tcl1 was localized in the cytoplasm and in the nucleus. Interestingly, Akt1 was also found in the nucleus when AKT1 was cotransfected with TCL1, suggesting that Tcl1 promotes the transport of Akt1 to the nucleus. These findings were supported by the intracellular localization of Akt1 or Tcl1 when Tcl1 or Akt1, respectively, were confined to the specific cellular compartments. Thus, we demonstrate that-Tcl1 is a cofactor of Akt1 that enhances Akt1 kinase activity and promotes its nuclear transport.

Original languageEnglish
Pages (from-to)3028-3033
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number7
Publication statusPublished - Mar 28 2000


ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Pekarsky, Y., Koval, A., Hallas, C., Bichi, R., Tresini, M., Malstrom, S., Russo, G., Tsichlis, P., & Croce, C. M. (2000). Tcl1 enhances Akt kinase activity and mediates its nuclear translocation. Proceedings of the National Academy of Sciences of the United States of America, 97(7), 3028-3033.