Journal article
Regulation and perturbation of Myocyte enhancer factor-2 (MEF-2) activity in Adult T-cell leukemia/lymphoma
The Journal of immunology (1950), v 202(1_Supplement), pp 75-75.16
01 May 2019
Abstract
Abstract HTLV-1 is a complex human retrovirus, an etiologic agent in causing malignant and intractable T-cell neoplasia. About 5% of the infected population would progress to acquiring a more aggressive form of non-Hodgkin’s lymphoma (NHL), termed as Adult T-cell leukemia/Lymphoma (ATLL). MEF-2 transcription factors are a family of genes that are involved in distinct functions in various tissues and isoforms of MEF-2 are 2A, 2B, 2C, 2D in mammals whose mutations are implicated in various cancers. Earlier studies from our lab delineated the role of MEF-2A in increased viral gene expression and inhibition of MEF-2A lead to the reduction in HTLV-1 viral replication and associated T-cell transformation. Presently, we have adopted to novel cyto-analytical techniques to quantitate gene transcripts and protein expression patterns at a single cell level for all the MEF-2 isoforms in different cell systems representing productive viral infection and/or ATLL. These studies revealed post-translationally modified, overexpression of MEF-2C and downregulated expression of MEF-2B which are known to be oncogene and tumor suppressor respectively. Similar results were obtained with a unique and specific HDAC-IIa inhibitor namely MC1568, which led to a dose-dependent cancer cell (but not normal) death in vitro while inhibiting viral proteins (Tax and HBZ) expression in vivo. In addition, exposure of HTLV-1-infected cells to MC1568 resulted in the activation of autophagy marker, LC3-II that is currently under investigation to a more in-depth mechanistic analysis.
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Details
- Title
- Regulation and perturbation of Myocyte enhancer factor-2 (MEF-2) activity in Adult T-cell leukemia/lymphoma
- Creators
- Kiran Kumar Madugula - Drexel UniversityCatherine DeMarino - George Mason UniversityAmanda Panfil - Ohio UniversityAlex Dobzanki - Drexel UniversityRashida Ginwala - Drexel UniversityZafar Khan - Drexel UniversityFatah Kashanchi - George Mason UniversityIsabelle Lemasson - East Carolina UniversityPatrick Green - Ohio UniversityEd Harhaj - Pennsylvania State UniversityPooja Jain - Drexel University
- Publication Details
- The Journal of immunology (1950), v 202(1_Supplement), pp 75-75.16
- Publisher
- American Association of Immunologists (AAI)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Other Identifier
- 991020545233404721