Fig. 1: Overview of the core-clock network and structure of the review.
From: Molecular mechanisms of tumour development in glioblastoma: an emerging role for the circadian clock
The figure shows an overview of the core clock network. The components of this network are interconnected by transcriptional and translational feedback loops. Briefly, CLOCK (Circadian locomoter output cycles protein kaput)/BMAL1 (Basic helix-loop-helix ARNT-like protein 1) heterodimers activate the transcription of target genes like PER (PERIOD) (PER1,2,3), CRY (CRYPTOCHROME) (CRY1,2), REV-ERB (Nuclear Receptor Subfamily 1 group D) (REV-ERBα,β), and ROR (RAR (Retinoic Acid Receptor) related Orphan Receptor) (RORα,β,γ) via binding to E-boxes on their promotor regions. CRY and PER proteins inhibit CLOCK/BMAL1. ROR and REV-ERB proteins compete for the binding to RORE elements on the promotor of BMAL1 to activate (ROR) or inhibit (REV-ERB) the transcription of BMAL19. The clock regulates hallmarks of cancer in GBM, in particular cell proliferation and cell cycle, apoptosis and survival, stemness, stress response, DNA-damage control and genomic instability, metabolic reprogramming, angiogenesis, tumour promoting inflammation and migration, invasion and metastasis, which are crucial for cancer progression. The pathways impacted by the clock are listed beneath each hallmark and will be discussed in further detail throughout this review. The figure was created with BioRender.com.
