DTA

Digital Theses Archive

 

Tesi etd-02042020-130458

Type of thesis
Dottorato
Author
BOLSHETTE, NITYANAND BHARAT
URN
etd-02042020-130458
Title
MYC-associated factor MAX is an essential repressor of the clock core network
Scientific disciplinary sector
Istituto di Scienze della Vita
Course
Istituto di Scienze della Vita - TRANSLATIONAL MEDICINE
Committee
relatore Dott. GRIMALDI, BENEDETTO
Keywords
  • Cancer
  • Molecular clock
  • MYC-associated factor X
  • Transcriptional regulation
Exam session start date
10/06/2020;
Availability
completa
Abstract
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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