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The post‐translational regulation of transcription factor EB (TFEB) in health and disease

Published version

Published version
Peer-reviewed

Repository DOI


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Authors

Takla, Michael 
Rubinsztein, David C  ORCID logo  https://orcid.org/0000-0001-5002-5263

Abstract

jats:titleAbstract</jats:title>jats:pTranscription factor EB (TFEB) is a basic helix–loop–helix leucine zipper transcription factor that acts as a master regulator of lysosomal biogenesis, lysosomal exocytosis, and macro‐autophagy. TFEB contributes to a wide range of physiological functions, including mitochondrial biogenesis and innate and adaptive immunity. As such, TFEB is an essential component of cellular adaptation to stressors, ranging from nutrient deprivation to pathogenic invasion. The activity of TFEB depends on its subcellular localisation, turnover, and DNA‐binding capacity, all of which are regulated at the post‐translational level. Pathological states are characterised by a specific set of stressors, which elicit post‐translational modifications that promote gain or loss of TFEB function in the affected tissue. In turn, the resulting increase or decrease in survival of the tissue in which TFEB is more or less active, respectively, may either benefit or harm the organism as a whole. In this way, the post‐translational modifications of TFEB account for its otherwise paradoxical protective and deleterious effects on organismal fitness in diseases ranging from neurodegeneration to cancer. In this review, we describe how the intracellular environment characteristic of different diseases alters the post‐translational modification profile of TFEB, enabling cellular adaptation to a particular pathological state.</jats:p>

Description

Funder: Rosetrees Trust (Rosetrees); doi: http://dx.doi.org/10.13039/501100000833


Funder: UK Dementia Research Institute (UK DRI); doi: http://dx.doi.org/10.13039/501100017510


Funder: MRC; doi: http://dx.doi.org/10.13039/100018645


Funder: Alzheimer's Research UK


Funder: Alzheimer's Society; doi: http://dx.doi.org/10.13039/501100000320


Funder: Cambridge University School of Clinical Medicine


Funder: James Baird Fund


Funder: F.E. Elmore Fund


Funder: Cambridge Commonwealth


Funder: European & International Trust


Funder: Nehru Trust for Cambridge University


Funder: Trinity‐Henry Barlow Scholarship

Keywords

mitochondria, TFEB, post‐translational modification, lysosome, autophagy

Journal Title

EMBO reports

Conference Name

Journal ISSN

1469-221X
1469-3178

Volume Title

Publisher

Springer Science and Business Media LLC
Sponsorship
NIHR ¦ NIHR Cambridge Biomedical Research Centre (NIHR Cambridge BRC) (BRC‐1215‐20014)