TFEB

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Transcription factor EB
Identifiers
Symbols TFEB ; ALPHATFEB; BHLHE35; TCFEB
External IDs OMIM600744 MGI103270 HomoloGene5182 GeneCards: TFEB Gene
RNA expression pattern
PBB GE TFEB 221866 at tn.png
PBB GE TFEB 50221 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 7942 21425
Ensembl ENSG00000112561 ENSMUSG00000023990
UniProt P19484 Q9R210
RefSeq (mRNA) NM_001167827 NM_001161722
RefSeq (protein) NP_001161299 NP_001155194
Location (UCSC) Chr 6:
41.65 – 41.7 Mb
Chr 17:
47.74 – 47.79 Mb
PubMed search [1] [2]

Transcription factor EB is a protein that in humans is encoded by the TFEB gene.[1][2]

Function[edit]

TFEB is a master gene for lysosomal biogenesis.[3] It encodes a transcription factor that coordinates expression of lysosomal hydrolases, membrane proteins and genes involved in autophagy.[3] Under aberrant lysosomal storage conditions such as in lysosomal storage diseases, TFEB translocated from the cytoplasm to the nucleus, resulting in the activation of its target genes.[3] TFEB overexpression in cultured cells induced lysosomal biogenesis and increased the degradation of complex molecules, such as glycosaminoglycans and the pathogenic protein that causes Huntington disease.[3] TFEB is activated by PGC1-alpha and promotes reduction of htt aggregation and neurotoxicity in a mouse model of Huntington disease.[4] Nuclear localization and activity of TFEB are regulated by serine phosphorylation and extracellular signal–regulated kinase 2 (ERK2) is the enzyme that phosphorylates TFEB. In turn, ERK2 is tuned to the levels of extracellular nutrients suggesting a coordination in regulation of autophagy and lysomal biogenesis and partnership of two distinct cellular organelles.[5] TFEB is activated in Trex1-deficient cells via inhibition of mTORC1 activity, resulting in an expanded lysosomal compartment.[6]

References[edit]

  1. ^ Carr CS, Sharp PA (Aug 1990). "A helix-loop-helix protein related to the immunoglobulin E box-binding proteins". Mol Cell Biol 10 (8): 4384–8. PMC 360994. PMID 2115126. 
  2. ^ "Entrez Gene: TFEB transcription factor EB". 
  3. ^ a b c d Sardiello M, Palmieri M, di Ronza A, Medina DL, Valenza M, Gennarino VA, Di Malta C, Donaudy F, Embrione V, Polishchuk RS, Banfi S, Parenti G, Cattaneo E, Ballabio A. (Jul 2009). "A gene network regulating lysosomal biogenesis and function". Science 325 (5939): 473–7. doi:10.1126/science.1174447. PMID 19556463. 
  4. ^ Tsunemi T, Ashe TD, Morrison BE, Soriano KR, Au J, Roque RA, Lazarowski ER, Damian VA, Masliah E, La Spada AR. (Jul 2012). "PGC-1α rescues Huntington's disease proteotoxicity by preventing oxidative stress and promoting TFEB function". Sci Transl Med 4 (142): 142ra97. doi:10.1126/scitranslmed.3003799. PMID 22786682. 
  5. ^ Settembre C, Di Malta C, Polito VA, Arencibia MG, Vetrini F, Erdin S, Erdin SU, Huynh T, Medina D, Colella P, Sardiello M, Rubinsztein DC, Ballabio A (May 2011). "TFEB Links Autophagy to Lysosomal Biogenesis". Science 332 (6036): 1429–33. doi:10.1126/science.1204592. PMID 21617040. 
  6. ^ Hasan M, Koch J, Rakheja D, Pattnaik AK, Brugarolas J, Dozmorov I, Levine B, Wakeland EK, Lee-Kirsch MA, Yan N. (January 2013). "Trex1 regulates lysosomal biogenesis and interferon-independent activation of antiviral genes". Nat Immunol. 14 (1): 61–71. doi:10.1038/ni.2475. PMID 23160154. 

Further reading[edit]