# Pathogenic hyperactivation of mTORC1 by cytoplasmic EP300 in Hutchinson-Gilford progeria syndrome

## TL;DR

This study shows that excess cytoplasmic EP300 causes mTORC1 overactivation and poor autophagy in a rare aging disease.

## Contribution

The paper reveals a new regulatory role of EP300 in the mTORC1/autophagy axis in a progeria context.

## Key findings

- Cytoplasmic EP300 overabundance leads to mTORC1 hyperactivation in progeria.
- Impaired autophagy is linked to mTORC1 overactivation in the disease.
- Nucleocytoplasmic shuttling of EP300 is regulated by nutrient availability.

## Abstract

In a recent issue in Nature Cell Biology, Sung Min Son
et al. unveil a novel layer in the regulation of the
mTORC1/autophagy axis by EP300 which can undergo nucleocytoplasmic shuttling in
response to alterations in nutrient availability. The study highlights that, in
Hutchinson-Gilford progeria syndrome, overabundant cytoplasmic EP300 results in
mTORC1 hyperactivation and impaired autophagy, potentially contributing to
premature and accelerated aging.