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

IF 4.1 Q2 CELL BIOLOGY

Cell Stress Pub Date : 2021-11-23 eCollection Date: 2021-12-01 DOI:10.15698/cst2021.12.260

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

引用次数: 0

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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p38 通过 TSC-mTORC1 通路调节肿瘤抑制因子 PDCD4。

程序性细胞死亡蛋白 4（PDCD4）作为肿瘤抑制因子和在免疫细胞中调节炎症过程发挥着重要功能。磷酸肌酸 3-激酶（PI3K）通过哺乳动物雷帕霉素靶复合物 1（mTORC1）促进 PDCD4 的降解。然而，可能调控 PDCD4 表达的其他途径大多尚未明确。在这项研究中，我们发现有丝分裂原激活蛋白激酶 p38 的激活促进了 PDCD4 在巨噬细胞和成纤维细胞中的降解。从机制上讲，我们确定了一条从 p38 及其底物 MAP 激酶激活蛋白激酶 2（MK2）到结节性硬化症复合体（TSC）的途径，以调控 mTORC1 依赖性的 PDCD4 降解。此外，我们还提供了证据，证明 TSC1 和 TSC2 通过独立于 mTORC1 的另一种机制调控 PDCD4 的表达。这些新数据扩展了我们对 PDCD4 表达如何受应激和营养传感途径调控的认识。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Stress Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (miscellaneous)

CiteScore

13.50

自引率

0.00%

发文量

审稿时长

15 weeks

期刊介绍： Cell Stress is an open-access, peer-reviewed journal that is dedicated to publishing highly relevant research in the field of cellular pathology. The journal focuses on advancing our understanding of the molecular, mechanistic, phenotypic, and other critical aspects that underpin cellular dysfunction and disease. It specifically aims to foster cell biology research that is applicable to a range of significant human diseases, including neurodegenerative disorders, myopathies, mitochondriopathies, infectious diseases, cancer, and pathological aging. The scope of Cell Stress is broad, welcoming submissions that represent a spectrum of research from fundamental to translational and clinical studies. The journal is a valuable resource for scientists, educators, and policymakers worldwide, as well as for any individual with an interest in cellular pathology. It serves as a platform for the dissemination of research findings that are instrumental in the investigation, classification, diagnosis, and therapeutic management of major diseases. By being open-access, Cell Stress ensures that its content is freely available to a global audience, thereby promoting international scientific collaboration and accelerating the exchange of knowledge within the research community.