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PLoS One. 2016 Sep 28;11(9):e0163328. doi: 10.1371/journal.pone.0163328. eCollection 2016.

Alternative Splice Variants Modulates Dominant-Negative Function of Helios in T-Cell Leukemia.

PloS one

Shaorong Zhao, Wei Liu, Yinghui Li, Pengjiang Liu, Shufang Li, Daolei Dou, Yue Wang, Rongcun Yang, Rong Xiang, Feifei Liu

Affiliations

  1. Department of Immunology, School of Medicine, Nankai University, Tianjin 300071, China.
  2. Tianjin Entry-Exit Inspection and Quarantine Bureau, Tianjin 300308, China.
  3. Department of Hematology, First-Central Hospital, Tianjin 300060, China.
  4. State Key Laboratory of Medical Chemical Biology, Tianjin 300070, China.
  5. Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Tianjin 300071, China.

PMID: 27681508 PMCID: PMC5040427 DOI: 10.1371/journal.pone.0163328

Abstract

The molecular defects which lead to multistep incidences of human T-cell leukemia have yet to be identified. The DNA-binding protein Helios (known as IKZF2), a member of the Ikaros family of Krüppel-like zinc-finger proteins, functions pivotally in T-cell differentiation and activation. In this study, we identify three novel short Helios splice variants which are T-cell leukemic specific, and demonstrate their dominant-negative function. We then test the cellular localization of distinct Helios isoforms, as well as their capability to form heterodimer with Ikaros, and the association with complexes comprising histone deacetylase (HDAC). In addition, the ectopic expression of T-cell leukemic Helios isoforms interferes with T-cell proliferation and apoptosis. The gene expression profiling and pathway analysis indicated the enrichment of signaling pathways essential for gene expression, translation, cell cycle checkpoint, and response to DNA damage stimulus. These data indicate the molecular function of Helios to be involved in the leukemogenesis and phenotype of T-cell leukemia, and also reveal Helios deregulation as a novel marker for T-cell leukemia.

Conflict of interest statement

The authors have declared that no competing interests exist.

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