Notch ankyrin domain: evolutionary rise of a thermodynamic sensor.

ABSTRACT: Notch signalling pathway plays a key role in metazoan biology by contributing to resolution of binary decisions in the life cycle of cells during development. Outcomes such as proliferation/differentiation dichotomy are resolved by transcriptional remodelling that follows a switch from Notch^on to Notch^off state, characterised by dissociation of Notch intracellular domain (NICD) from DNA-bound RBPJ. Here we provide evidence that transitioning to the Notch^off state is regulated by heat flux, a phenomenon that aligns resolution of fate dichotomies to mitochondrial activity. A combination of phylogenetic analysis and computational biochemistry was utilised to disclose structural adaptations of Notch1 ankyrin domain that enabled function as a sensor of heat flux

SUBMITTER: Vujovic F 

PROVIDER: S-EPMC9118731 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature