Research ArticleCell Biology

The Transcription Factor TFEB Links mTORC1 Signaling to Transcriptional Control of Lysosome Homeostasis

Sci. Signal.  12 Jun 2012:
Vol. 5, Issue 228, pp. ra42
DOI: 10.1126/scisignal.2002790

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Sensing Lysosomal Status

Lysosomes clear cells of damaged organelles, cellular debris, and internalized materials. Lysosomal biogenesis requires the transcription factor TFEB, and Roczniak-Ferguson et al. investigated the mechanisms by which lysosomal status controlled the activity of TFEB. They found that TFEB interacted with mTOR (mechanistic target of rapamycin), a kinase that localizes to lysosomes. The mTOR-dependent phosphorylation of TFEB caused TFEB to interact with 14-3-3 proteins, which led to the retention of the transcription factor in the cytoplasm. When lysosomal function was inhibited, TFEB no longer interacted with mTOR, was dephosphorylated, and translocated to the nucleus. Thus, the localization (and thus activity) of TFEB is determined by mTOR-mediated phosphorylation, which in turn reflects lysosomal status.

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