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Increased unfolded protein responses caused by MED17 mutations

Takeshi Terabayashi1, Satoru Hashimoto2,3

  • 1Department of Pharmacology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama, Yufu, Oita, 879-5593, Japan.

Neurogenetics
|August 15, 2021
PubMed

Insights

Mutations in MED17 can cause rare genetic disorders. This study found increased unfolded protein responses (UPRs) in cells from patients, suggesting UPRs contribute to disease symptoms.

Area of Science:

  • Genetics
  • Molecular Biology
  • Cellular Biology

Background:

  • Mediator (MED) complex regulates gene expression.
  • Mutations in MED subunits are linked to various diseases.
  • MED17 mutations cause rare autosomal recessive disorders like microcephaly and intellectual disability.

Purpose of the Study:

  • To investigate the cellular impact of MED17 mutations.
  • To elucidate the genotype-phenotype association in MED17-related disorders.
  • To understand the role of unfolded protein responses (UPRs) in MED17 mutations.

Main Methods:

  • Analysis of patient-derived fibroblasts.
  • Measurement of unfolded protein response (UPR) gene expression.
  • Assessment of protein phosphorylation levels.

Main Results:

  • Fibroblasts from patients with MED17 mutations showed increased UPRs.
  • UPR genes CHOP and ATF4 expression was upregulated.
  • Basal phosphorylation of eIF2a was elevated in patient cells.

Conclusions:

  • MED17 mutations are associated with increased unfolded protein responses.
  • Elevated UPRs may contribute to the clinical phenotype of MED17-related disorders.
  • Further research is needed to fully understand the genotype-phenotype correlation.
Keywords:
Choreiform movementMED17Mediator complexUnfold protein responses

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