Tesi etd-02042020-130458
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Tipo di tesi
Dottorato
Autore
BOLSHETTE, NITYANAND BHARAT
URN
etd-02042020-130458
Titolo
MYC-associated factor MAX is an essential repressor of the clock core network
Settore scientifico disciplinare
Istituto di Scienze della Vita
Corso di studi
Istituto di Scienze della Vita - TRANSLATIONAL MEDICINE
Commissione
relatore Dott. GRIMALDI, BENEDETTO
Parole chiave
- Cancer
- Molecular clock
- MYC-associated factor X
- Transcriptional regulation
Data inizio appello
10/06/2020;
Disponibilità
completa
Riassunto analitico
The molecular core clock network is based on interconnected feedback loops linking activators and repressors of clock-controlled genes. This study reveals that the MYC-Associated factor X, MAX, plays an essential repressive role in this transcriptional-translational feedback loop. MAX operates through a MYC-independent binding to E-box regions within the promoters of circadian BMAL1 targets. This clock function of MAX is essential for maintaining a proper circadian rhythm but separated by the role of MAX as a partner of MYC in controlling cell proliferation. We also identified MAX Network Transcriptional Repressor, MNT, as a fundamental partner of MAX-mediated circadian regulation. In conclusion, our data has demonstrated MAX is an essential part of the core molecular clock and keeps the balance between clock activators and repressors. Accordingly, alteration of MAX transcriptional complexes may contribute to circadian dysfunction in pathological contexts.
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