Context-dependent Dysregulation of Transcription by Mutant Huntingtin
نویسندگان
چکیده
منابع مشابه
Altered histone monoubiquitylation mediated by mutant huntingtin induces transcriptional dysregulation.
Although transcriptional dysregulation is a critical pathogenic mechanism in Huntington's disease (HD), it is still not known how mutant huntingtin causes it. Here we show that alteration of histone monoubiquitylation is a key mechanism. Disrupted interaction of huntingtin with Bmi-1, a component of the hPRC1L E3 ubiquitin ligase complex, increases monoubiquityl histone H2A (uH2A) levels in a c...
متن کاملMutant huntingtin causes context-dependent neurodegeneration in mice with Huntington's disease.
Huntington's disease (HD) mouse models that express N-terminal huntingtin fragments show rapid disease progression and have been used for developing therapeutics. However, light microscopy reveals no significant neurodegeneration in these mice. It remains unclear how mutant huntingtin induces neurodegeneration. Using caspase staining, terminal deoxynucleotidyl transferase-mediated biotinylated ...
متن کاملChromatin dysregulation by mutant p53
The TP53 gene, which encodes a DNA sequencedependent transcriptional regulator, is arguably the most frequently mutated gene in human cancer. Whereas wildtype p53 is restricted to its cognate DNA binding sites, mutant p53 (via mutation in the DNA binding domain) is no longer constrained to specific genomic sites. Mutant p53 proteins therefore cannot effectively mediate wildtype p53 tumor suppre...
متن کاملHypothalamic overexpression of mutant huntingtin causes dysregulation of brown adipose tissue
Expression of mutant huntingtin (htt) protein has been shown to cause metabolic imbalance in animal models of Huntington disease (HD). The pathways involved are not fully understood but dysfunction of both the hypothalamus and brown adipose tissue (BAT) has been implicated. Here we show that targeted expression of mutant HTT in the hypothalamus leads to loss of the A13 dopaminergic cell group l...
متن کاملCdk5 phosphorylation of huntingtin reduces its cleavage by caspases: implications for mutant huntingtin toxicity
untington’s disease (HD) is a neurodegenerative disorder caused by an expanded polyglutamine (polyQ) tract in the huntingtin (htt) protein. Mutant htt toxicity is exposed after htt cleavage by caspases and other proteases release NH 2 -terminal fragments containing the polyQ expansion. Here, we show htt interacts and colocalizes with cdk5 in cellular membrane fractions. Cdk5 phosphorylates htt ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Journal of Biological Chemistry
سال: 2006
ISSN: 0021-9258
DOI: 10.1074/jbc.m607839200