TFEB (Transcription Factor EB)
TFEB is the master transcriptional regulator of lysosomal biogenesis and autophagy genes. Active mTORC1 phosphorylates TFEB, retaining it in the cytoplasm and preventing nuclear tr...
Classification
Category: Downstream effector / lysosomal-autophagy transcription factor
Aliases: none recorded
Relationship to mTOR complexes: Direct mTORC1 substrate; downstream of mTORC1 — see mTORC1 vs mTORC2 for the full complex-level map.
Summary
TFEB is the master transcriptional regulator of lysosomal biogenesis and autophagy genes. Active mTORC1 phosphorylates TFEB, retaining it in the cytoplasm and preventing nuclear translocation. When mTORC1 activity falls, TFEB is dephosphorylated, translocates to the nucleus, and upregulates lysosomal/autophagy gene transcription.
| Upstream of | Autophagic Flux |
| Downstream of | MTORC1 |
- mTORC1 (active) phosphorylates TFEB, suppressing its nuclear translocation and transcriptional activity
- Upon nuclear translocation, TFEB drives transcription of lysosomal biogenesis genes and autophagy-machinery genes (the CLEAR gene network)
- TFEB localization (cytoplasmic vs nuclear) is one of the static assay markers listed on the pathway/assay-reference table; like ULK1 phosphorylation and LC3-II/p62 levels, TFEB localization at a single time point is NOT the same as measured autophagic flux.
- TFEB and ULK1 are the two mTORC1 outputs on this dataset's map most directly tied to autophagy; S6K1 and 4E-BP1 instead drive protein synthesis -- the two branches move in opposite functional directions when mTORC1 activity changes.
Source tier
Tier 2 · Biological synthesis (author-cluster reviews, not primary trial data) Reference synthesis attributed in the brief to the Saxton & Sabatini; Laplante & Sabatini; and Liu & Sabatini mTOR review literature (author-cluster attribution, tier 2, brief ยง4). Exact article-level PMID/DOI not supplied in the sourcing brief and is not fabricated here.