Open Access

Nuclear lymphocyte-specific protein tyrosine kinase and its interaction with CR6-interacting factor 1 promote the survival of human leukemic T cells

  • Authors:
    • Shahrooz Vahedi
    • Fu-Yu Chueh
    • Sujoy Dutta
    • Bala Chandran
    • Chao-Lan Yu
  • View Affiliations

  • Published online on: May 19, 2015     https://doi.org/10.3892/or.2015.3990
  • Pages: 43-50
  • Copyright: © Vahedi et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Overexpression and hyperactivation of lymphocyte-specific protein tyrosine kinase (Lck) have been associated with leukemia development. We previously showed that, other than its known function as a cytoplasmic signal transducer, Lck also acts as a nuclear transcription factor in mouse leukemic cells. In the present study, we demonstrated the presence of nuclear Lck in human leukemic T cells and in primary cells. We further established a positive correlation between Lck nuclear localization and its kinase activity. Proteomic analysis identified CR6-interacting factor 1 (CRIF1) as one of the Lck-interacting proteins. CRIF1 and Lck association in the nucleus was confirmed both by immunofluorescence microscopy and co-immunoprecipitation in human leukemic T cells. Close-range interaction between Lck and CRIF1 was validated by in situ proximity ligation assay (PLA). Consistent with the role of nuclear CRIF1 as a tumor suppressor, CRIF1 silencing promotes leukemic T cell survival in the absence of growth factors. This protective effect can be recapitulated by endogenous Lck or reconstituted Lck in leukemic T cells. All together, our results support a novel function of nuclear Lck in promoting human leukemic T cell survival through interaction with a tumor suppressor. It has important implications in defining a paradigm shift of non-canonical protein tyrosine kinase signaling.
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July-2015
Volume 34 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Vahedi S, Chueh F, Dutta S, Chandran B and Yu C: Nuclear lymphocyte-specific protein tyrosine kinase and its interaction with CR6-interacting factor 1 promote the survival of human leukemic T cells. Oncol Rep 34: 43-50, 2015
APA
Vahedi, S., Chueh, F., Dutta, S., Chandran, B., & Yu, C. (2015). Nuclear lymphocyte-specific protein tyrosine kinase and its interaction with CR6-interacting factor 1 promote the survival of human leukemic T cells. Oncology Reports, 34, 43-50. https://doi.org/10.3892/or.2015.3990
MLA
Vahedi, S., Chueh, F., Dutta, S., Chandran, B., Yu, C."Nuclear lymphocyte-specific protein tyrosine kinase and its interaction with CR6-interacting factor 1 promote the survival of human leukemic T cells". Oncology Reports 34.1 (2015): 43-50.
Chicago
Vahedi, S., Chueh, F., Dutta, S., Chandran, B., Yu, C."Nuclear lymphocyte-specific protein tyrosine kinase and its interaction with CR6-interacting factor 1 promote the survival of human leukemic T cells". Oncology Reports 34, no. 1 (2015): 43-50. https://doi.org/10.3892/or.2015.3990