PUBLICATION
LOXL2 Oxidizes Methylated TAF10 and Controls TFIID-Dependent Genes during Neural Progenitor Differentiation
- Authors
- Iturbide, A., Pascual-Reguant, L., Fargas, L., Cebrià, J.P., Alsina, B., García de Herreros, A., Peiró, S.
- ID
- ZDB-PUB-150512-8
- Date
- 2015
- Source
- Molecular Cell 58(5): 755-66 (Journal)
- Registered Authors
- Alsina, Berta
- Keywords
- none
- MeSH Terms
-
- Protein Processing, Post-Translational*
- HEK293 Cells
- Neural Stem Cells/physiology*
- Amino Acid Oxidoreductases/physiology*
- Cell Differentiation*
- Epigenesis, Genetic
- TATA-Binding Protein Associated Factors/metabolism*
- Animals
- Zebrafish
- Methylation
- Humans
- Oxidation-Reduction
- Transcription Factor TFIID/metabolism
- Transcription Factor TFIID/physiology*
- PubMed
- 25959397 Full text @ Mol. Cell
Citation
Iturbide, A., Pascual-Reguant, L., Fargas, L., Cebrià, J.P., Alsina, B., García de Herreros, A., Peiró, S. (2015) LOXL2 Oxidizes Methylated TAF10 and Controls TFIID-Dependent Genes during Neural Progenitor Differentiation. Molecular Cell. 58(5):755-66.
Abstract
Protein function is often regulated and controlled by posttranslational modifications, such as oxidation. Although oxidation has been mainly considered to be uncontrolled and nonenzymatic, many enzymatic oxidations occur on enzyme-selected lysine residues; for instance, LOXL2 oxidizes lysines by converting the ε-amino groups into aldehyde groups. Using an unbiased proteomic approach, we have identified methylated TAF10, a member of the TFIID complex, as a LOXL2 substrate. LOXL2 oxidation of TAF10 induces its release from its promoters, leading to a block in TFIID-dependent gene transcription. In embryonic stem cells, this results in the inactivation of the pluripotency genes and loss of the pluripotent capacity. During zebrafish development, the absence of LOXL2 resulted in the aberrant overexpression of the neural progenitor gene Sox2 and impaired neural differentiation. Thus, lysine oxidation of the transcription factor TAF10 is a controlled protein modification and demonstrates a role for protein oxidation in regulating pluripotency genes.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping