Inhibition of Myc transcriptional activity by a mini‐protein based upon Mxd1
| Autor: | Angie Sun, Brian Hall, Jennifer O'Neil, Abbas Walji, Claudio Mapelli, Michael J. Hohn, Mark J Demma |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
animal structures
Transcription Genetic Biophysics Biochemistry Cell Line Proto-Oncogene Proteins c-myc 03 medical and health sciences chemistry.chemical_compound Downregulation and upregulation Structural Biology Transcription (biology) Genetics Humans Amino Acid Sequence Promoter Regions Genetic Molecular Biology Gene Transcription factor Cell Proliferation 030304 developmental biology Cell Nucleus 0303 health sciences Oncogene Basic Helix-Loop-Helix Leucine Zipper Transcription Factors Cell growth 030302 biochemistry & molecular biology Promoter Cell Biology Peptide Fragments Cell biology Repressor Proteins Basic-Leucine Zipper Transcription Factors chemistry Pol1 Transcription Initiation Complex Proteins Cell Nucleolus DNA |
| Zdroj: | FEBS Letters. 594:1467-1476 |
| ISSN: | 1873-3468 0014-5793 |
| DOI: | 10.1002/1873-3468.13759 |
| Popis: | Myc, a transcription factor with oncogenic activity, is upregulated by amplification, translocation, and mutation of the cellular pathways that regulate its stability. Inhibition of the Myc oncogene by various modalities has had limited success. One Myc inhibitor, Omomyc, has limited cellular and in vivo activity. Here, we report a mini-protein, referred to as Mad, which is derived from the cellular Myc antagonist Mxd1. Mad localizes to the nucleus in cells and is 10-fold more potent than Omomyc in inhibiting Myc-driven cell proliferation. Similar to Mxd1, Mad also interacts with Max, the binding partner of Myc, and with the nucleolar upstream binding factor. Mad binds to E-Box DNA in the promoters of Myc target genes and represses Myc-mediated transcription to a greater extent than Omomyc. Overall, Mad appears to be more potent than Omomyc both in vitro and in cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text