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

Shahrooz Vahedi, Fu Yu Chueh, Sujoy Dutta, Bala Chandran, Chao Lan Yu*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

4 Scopus citations

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.

Original languageEnglish
Pages (from-to)431-438
Number of pages8
JournalOncology Reports
Volume34
Issue number1
DOIs
StatePublished - 01 07 2015
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2015, Spandidos Publications. All rights reserved.

Keywords

  • CRIF1
  • Cell survival
  • Leukemia
  • Lymphocyte-specific protein tyrosine kinase
  • Non-canonical signaling
  • Proximity ligation assay

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