Increased unfolded protein responses caused by MED17 mutations
- 15 August 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in neurogenetics
- Vol. 22 (4), 353-357
- https://doi.org/10.1007/s10048-021-00661-6
Abstract
Mediator (MED) is a key regulator of protein-coding gene expression, and mutations in MED subunits are associated with a broad spectrum of diseases. Because mutations in MED17 result in autosomal recessive disorders, including microcephaly, intellectual disability, epilepsy, and ataxia, which are barely reported, with only three case reports to date, genotype–phenotype association should be elucidated. Here, we investigated the impact of MED17 mutations on cellular responses and found increased unfolded protein responses (UPRs) in fibroblasts derived from Japanese patients with MED17 mutations. The expression of the UPR genes CHOP and ATF4 was upregulated, and the phosphorylation of eIF2a was basally increased in patients’ cells. Based on our findings, we propose that increased UPRs caused by MED17 mutations might contribute to the clinical phenotype.Keywords
Funding Information
- Japan Society for the Promotion of Science (15K06758, 19H04266)
This publication has 22 references indexed in Scilit:
- Mediator MED23 regulates basal transcription in vivo via an interaction with P-TEFbTranscription, 2013
- Novel Role for Mediator Complex Subunit Srb5/Med18 in Termination of Transcription*Online Journal of Public Health Informatics, 2011
- MED23 Mutation Links Intellectual Disability to Dysregulation of Immediate Early Gene ExpressionScience, 2011
- Human Mediator Subunit MED26 Functions as a Docking Site for Transcription Elongation FactorsCell, 2011
- Function and regulation of the Mediator complexCurrent Opinion in Genetics & Development, 2011
- Infantile Cerebral and Cerebellar Atrophy Is Associated with a Mutation in the MED17 Subunit of the Transcription Preinitiation Mediator ComplexAmerican Journal of Human Genetics, 2010
- Identification of the variant Ala335Val of MED25 as responsible for CMT2B2: molecular data, functional studies of the SH3 recognition motif and correlation between wild-type MED25 and PMP22 RNA levels in CMT1A animal modelsneurogenetics, 2009
- A Coated Vesicle-associated Kinase of 104 kDa (CVAK104) Induces Lysosomal Degradation of Frizzled 5 (Fzd5)Online Journal of Public Health Informatics, 2009
- Rrs1 Is Involved in Endoplasmic Reticulum Stress Response in Huntington DiseaseOnline Journal of Public Health Informatics, 2009
- Identification of the variant Ala335Val of MED25 as responsible for CMT2B2: molecular data, functional studies of the SH3 recognition motif and correlation between wild-type MED25 and PMP22 RNA levels in CMT1A animal modelsneurogenetics, 2009