Table of contents

Volume 5, Issue 12, pp. 176 - 182, December 2021

Issue cover
Cover: "Icy Neurons" by Andreas Zimmermann. The cover is published under the CC BY 4.0 license. Enlarge issue cover

Research Articles

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

Clarissa Braun, Karl Katholnig, Christopher Kaltenecker, Monika Linke, Nyamdelger Sukhbaatar, Markus Hengstschläger and Thomas Weichhart

page 176-182 | 10.15698/cst2021.12.260 | Full text | PDF | Abstract

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 degradation of PDCD4. Moreover, we provide evidence that TSC1 and TSC2 regulate PDCD4 expression via an additional mechanism independent of mTORC1. These novel data extend our knowledge of how PDCD4 expression is regulated by stress- and nutrient-sensing pathways.

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