| Gene Name | MEF2A |
| HF Protein Name | Myocyte-specific enhancer factor 2A |
| HF Function | Essential for viral replication |
| Uniprot ID | Q02078 |
| Protein Sequence | View Fasta Sequence |
| NCBI Gene ID | 4205 |
| Host Factor (HF) Name in Paper | MEF2 |
| Gene synonyms | MEF2 |
| Ensemble Gene ID | ENSG00000068305 |
| Ensemble Transcript | ENST00000338042 [Q02078-6];ENST00000354410 [Q02078-5];ENST00000449277 [Q02078-8];ENST00000557785 [Q02078-6];ENST00000557942 [Q02078-2];ENST00000558812 [Q02078-7] |
| KEGG ID | Go to KEGG Database |
| Gene Ontology ID(s) | GO:0000002, GO:0000122, GO:0000165, GO:0000790, GO:0000977, GO:0000978, GO:0000981, GO:0001077, GO:0001085, GO:0001105, GO:0003682, GO:0003700, GO:0003705, GO:0005634, GO:0005654, GO:0005667, GO:0005829, GO:0006351, GO:0006915, GO:0007507, GO:0007517, GO:0010613, GO:0019901, GO:0033613, GO:0035035, GO:0042826, GO:0043565, GO:0045944, GO:0046332, GO:0046982, GO:0048311, GO:0048813, GO:0051149, GO:0055005, GO:0061337, GO:0070375, GO:0071277, |
| MINT ID | Q02078 |
| STRING | Click to see interaction map |
| GWAS Analysis | Click to see gwas analysis |
| OMIM ID | 600660 |
| PANTHER ID | N.A. |
| PDB ID(s) | 1C7U, 1EGW, 1LEW, 3KOV, 3MU6, 3P57, 6BYY, 6BZ1, |
| pfam ID | PF12347, PF00319, |
| Drug Bank ID | N.A., |
| ChEMBL ID | N.A. |
| Organism | Homo sapiens (Human) |
| Virus Name | Human T-lymphotropic virus1 |
| Virus Short Name | HTLV-I |
| Order | Unassigned |
| Virus Family | Retroviridae |
| Virus Subfamily | Orthoretrovirinae |
| Genus | Deltaretrovirus |
| Species | Human T-lymphotropic virus 1 |
| Host | Vertebrates |
| Cell Tropism | Lymphocytes |
| Associated Disease | Adult t-cell leukemia |
| Mode of Transmission | Sexual contact, maternal-neonatal |
| VIPR DB link | N.A. |
| ICTV DB link | https://talk.ictvonline.org/ictv-reports/ictv_9th_report/reverse-transcribing-dna-and-rna-viruses-2011/w/rt_viruses/161/retroviridae |
| Virus Host DB link | http://www.genome.jp/virushostdb/view/?virus_lineage=Retroviridae |
| Paper Title | Myocyte enhancer factor (MEF)-2 plays essential roles in T-cell transformation associated with HTLV-1 infection by stabilizing complex between Tax and CREB |
| Author's Name | Pooja Jain, Alfonso Lavorgna, Mohit Sehgal, Linlin Gao, Rashida Ginwala, Divya Sagar, Edward W Harhaj and Zafar K Khan |
| Journal Name | Retrovirology |
| Pubmed ID | 25809782 |
| Abstract | BACKGROUND: The exact molecular mechanisms regarding HTLV-1 Tax-mediated viral gene expression and CD4 T-cell transformation have yet to be fully delineated. Herein, utilizing virus-infected primary CD4+ T cells and the virus-producing cell line, MT-2, we describe the involvement and regulation of Myocyte enhancer factor-2 (specifically MEF-2A) during the course of HTLV-1 infection and associated disease syndrome. RESULTS: Inhibition of MEF-2 expression by shRNA and its activity by HDAC9 led to reduced viral replication and T-cell transformation in correlation with a heightened expression of MEF-2 in ATL patients. Mechanistically, MEF-2 was recruited to the viral promoter (LTR, long terminal repeat) in the context of chromatin, and constituted Tax/CREB transcriptional complex via direct binding to the HTLV-1 LTR. Furthermore, an increase in MEF-2 expression was observed upon infection in an extent similar to CREB (known Tax-interacting transcription factor), and HATs (p300, CBP, and p/CAF). Confocal imaging confirmed MEF-2 co-localization with Tax and these proteins were also shown to interact by co-immunoprecipitation. MEF-2 stabilization of Tax/CREB complex was confirmed by a novel promoter-binding assay that highlighted the involvement of NFAT (nuclear factor of activated T cells) in this process via Tax-mediated activation of calcineurin (a calcium-dependent serine-threonine phosphatase). MEF-2-integrated signaling pathways (PI3K/Akt, NF-κB, MAPK, JAK/STAT, and TGF-beta) were also activated during HTLV-1 infection of primary CD4+ T cells, possibly regulating MEF-2 activity. CONCLUSIONS: We demonstrate the involvement of MEF-2 in Tax-mediated LTR activation, viral replication, and T-cell transformation in correlation with its heightened expression in ATL patients through direct binding to DNA within the HTLV-1 LTR. |
| Used Model | primary CD4+ T cells |
| DOI | 10.1186/s12977-015-0140-1 |
