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Identification of BERP (brain-expressed RING finger protein) as a p53 target gene that modulates seizure susceptibility through interacting with GABA(A) receptors.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2010 Jun 29; Vol. 107 (26), pp. 11883-8. Date of Electronic Publication: 2010 Jun 11. - Publication Year :
- 2010
-
Abstract
- p53 is a central player in responses to cellular stresses and a major tumor suppressor. The identification of unique molecules within the p53 signaling network can reveal functions of this important transcription factor. Here, we show that brain-expressed RING finger protein (BERP) is a gene whose expression is up-regulated in a p53-dependent manner in human cells and in mice. We generated BERP-deficient mice by gene targeting and demonstrated that they exhibit increased resistance to pentylenetetrazol-induced seizures. Electrophysiological and biochemical studies of cultured cortical neurons of BERP-deficient mice showed a decrease in the amplitude of GABA(A) receptor (GABA(A)R)-mediated miniature inhibitory postsynaptic currents as well as reduced surface protein expression of GABA(A)Rs containing the gamma2-subunit. However, BERP deficiency did not decrease GABA(A)Rgamma2 mRNA levels, raising the possibility that BERP may act at a posttranscriptional level to regulate the intracellular trafficking of GABA(A)Rs. Our results indicate that BERP is a unique p53-regulated gene and suggest a role for p53 within the central nervous system.
- Subjects :
- Animals
Base Sequence
Cells, Cultured
Convulsants toxicity
DNA Primers genetics
Genes, p53
Humans
Male
Mice
Mice, Knockout
Nerve Tissue Proteins deficiency
Neurons metabolism
Pentylenetetrazole toxicity
RNA, Messenger genetics
RNA, Messenger metabolism
Receptors, GABA-A genetics
Seizures chemically induced
Up-Regulation
Carrier Proteins genetics
Nerve Tissue Proteins genetics
Receptors, GABA-A metabolism
Seizures genetics
Seizures metabolism
Tumor Suppressor Protein p53 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 107
- Issue :
- 26
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 20543135
- Full Text :
- https://doi.org/10.1073/pnas.1006529107