MTORC1 – Cell Stress

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

Mechanistic target of rapamycin complex 1 (mTORC1) is a multiprotein complex that serves as a pivotal regulator of cell growth, protein synthesis, metabolism and autophagy [1][2]. This complex compromises mTOR … Read more

p38 regulates the tumor suppressor PDCD4 via the TSC-mTORC1 pathway

Programmed cell death protein 4 (PDCD4) exerts critical functions as tumor suppressor and in immune cells to regulate inflammatory processes. The phosphoinositide 3-kinase (PI3K) promotes degradation of PDCD4 via mammalian target of rapamycin complex 1 (mTORC1). However, additional pathways that may regulate PDCD4 expression are largely ill-defined. In this study, we have found that activation of the mitogen-activated protein kinase p38 promoted degradation of PDCD4 in macrophages and fibroblasts. Mechanistically, we identified a pathway from p38 and its substrate MAP kinase-activated protein kinase 2 (MK2) to the tuberous sclerosis complex (TSC) to regulate mTORC1-dependent (…)

GRASPing the unconventional secretory machinery to bridge cellular stress signaling to the extracellular proteome

Part of the cellular response to stress is an evolutionarily conserved, poorly-understood process called unconventional protein secretion (UPS). Although cells shut down conventional/bulk secretion to save resources upon stress, UPS … Read more

TFEB-mTORC1 feedback loop in metabolism and cancer

Everyday most organisms face the requirement to adapt their metabolic cues to the fluctuation of nutrient resources into the environment. When nutrients are abundant cells activate anabolic pathways, such as … Read more