ArticleHuman molecular genetics2017
MeCP2_E1 N-terminal modifications affect its degradation rate and are disrupted by the Ala2Val Rett mutation.
Article in Human molecular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- N-Terminal Variant p.Ala2Val in X-Linked Dyskeratosis Congenita Gene (DKC1) Disrupts Its Post-Translational Modification and Nucleolar Localization.Molecular genetics & genomic medicine · 2026Article
- N-terminal acetylation controls multiple functional aspects of the influenza A virus ribonuclease PA-X.Journal of virology · 2026Article
- MeCP2 functions as a DNA methylation reader in immune homeostasis and cancer.Frontiers in epigenetics and epigenomics · 2026Review
- N-terminal acetylation controls multiple functional aspects of the influenza A virus ribonuclease PA-X.bioRxiv : the preprint server for biology · 2025Article
- InPathogens (Basel, Switzerland) · 2025Article
- Testing the PEST hypothesis using relevant Rett mutations in MeCP2 E1 and E2 isoforms.Human molecular genetics · 2024Article
- Biallelic USP14 variants cause a syndromic neurodevelopmental disorder.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Article
- Nuclease-free precise genome editing corrects MECP2 mutations associated with Rett syndrome.Frontiers in genome editing · 2024Article
- A Severity Comparison between Italian and Israeli Rett Syndrome Cohorts.Diagnostics (Basel, Switzerland) · 2023Article
- Wide spectrum of neuronal and network phenotypes in human stem cell-derived excitatory neurons with Rett syndrome-associated MECP2 mutations.Translational psychiatry · 2022Article
- Genetics behind Cerebral Disease with Ocular Comorbidity: Finding Parallels between the Brain and Eye Molecular Pathology.International journal of molecular sciences · 2022Review
- Sleep Disorders in Rett Syndrome and Rett-Related Disorders: A Narrative Review.Frontiers in neurology · 2022Review
- Stabilization Effect of Intrinsically Disordered Regions on Multidomain Proteins: The Case of the Methyl-CpG Protein 2, MeCP2.Biomolecules · 2021Article
- Role of DNA Methyl-CpG-Binding Protein MeCP2 in Rett Syndrome Pathobiology and Mechanism of Disease.Biomolecules · 2021Review
- MeCP2: The Genetic Driver of Rett Syndrome Epigenetics.Frontiers in genetics · 2021Review
- N-Terminal Acetylation Stabilizes SIGMA FACTOR BINDING PROTEIN1 Involved in Salicylic Acid-Primed Cell Death.Plant physiology · 2020Article
- MeCP2 and Chromatin Compartmentalization.Cells · 2020Review
- The MeCP2E1/E2-BDNF-Frontiers in cell and developmental biology · 2020Article
- MeCP2-E1 isoform is a dynamically expressed, weakly DNA-bound protein with different protein and DNA interactions compared to MeCP2-E2.Epigenetics & chromatin · 2019Article
- Spotlight on protein N-terminal acetylation.Experimental & molecular medicine · 2018Review
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Methyl CpG-binding protein 2 (MeCP2), the mutated protein in Rett syndrome (RTT), is a crucial chromatin-modifying and gene-regulatory protein that has two main isoforms (MeCP2_E1 and MeCP2_ E2) due to the alternative splicing and switching between translation start codons in exons one and two. Functionally, these two isoforms appear to be virtually identical; however, evidence suggests that only MeCP2_E1 is relevant to RTT, including a single RTT missense mutation in exon 1, Ala2Val. Here, we show that N-terminal co- and post-translational modifications differ for MeCP2_E1 and MeCP2_E1-Ala2Val, which result in different protein degradation rates in vitro. We report complete N-methionine excision (NME) for MeCP2_E1 and evidence of excision of multiple alanine residues from the N-terminal polyalanine stretch. For MeCP2_E1-Ala2Val, we observed only partial NME and N-acetylation (NA) of either methionine or valine. The localization of MeCP2_E1 and co-localization with chromatin appear to be unaffected by the Ala2Val mutation. However, a higher proteasomal degradation rate was observed for MeCP2_E1-Ala2Val compared with that for wild type MeCP2_E1. Thus, the etiopathology of Ala2Val is likely due to a reduced bio-availability of MeCP2 because of the faster degradation rate of the unmodified defective protein. Our data on the effects of the Ala2Val mutation on N-terminal modifications of MeCP2 may be applicable to Ala2Val mutations in other disease genes for which no etiopathological mechanism has been established.
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