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Non-canonical mTORC1 signaling at the lysosome

期刊

TRENDS IN CELL BIOLOGY
卷 32, 期 11, 页码 920-931

出版社

CELL PRESS
DOI: 10.1016/j.tcb.2022.04.012

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资金

  1. Italian Telethon Foundation
  2. Associazione Italiana per la Ricerca sul Cancro (AIRC) [MFAG-23538, IG-22103, 5x1000-21051]
  3. Ministero dell'Universita e della Ricerca (MIUR) [PRIN 2017YF9FBS, PRIN 2017E5L5P3]
  4. Worldwide Cancer Research [21-0278]
  5. Kidney Cancer Association
  6. European Research Council [694282]
  7. European Research Council (ERC) [694282] Funding Source: European Research Council (ERC)

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The mTORC1 signaling pathway integrates multiple environmental cues to regulate cell growth and metabolism. Recent studies have revealed a 'non-canonical' signaling pathway of mTORC1 that controls the function of MiT-TFE transcription factors, key regulators of cell metabolism, and responds to stimuli that converge on the lysosomal surface.
Themechanistic target of rapamycin complex 1 (mTORC1) signaling hub integrates multiple environmental cues to modulate cell growth and metabolism. Over the past decade considerable knowledge has been gained on the mechanisms modulating mTORC1 lysosomal recruitment and activation. However, whether and how mTORC1 is able to elicit selective responses to diverse signals has remained elusive until recently. We discuss emerging evidence for a 'non-canonical' mTORC1 signaling pathway that controls the function of microphthalmia/transcription factor E (MiT-TFE) transcription factors, key regulators of cell metabolism. This signaling pathway is mediated by a specific mechanism of substrate recruitment, and responds to stimuli that appear to converge on the lysosomal surface. We discuss the relevance of this pathway in physiological and disease conditions.

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