Dataset Information

Hdac4 interactome in Huntington's Disease

ABSTRACT: Hdac4 has been found to modulate symptoms in Huntington's Disease (HD) mouse models through an uknown mechanism unrelated to any enzymatic activity. We investigated the protein-protein interactions to gain insight into the role of Hdac4 in HD.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

DISEASE(S): Huntington Disease

SUBMITTER: Joel Federspiel

LAB HEAD: Ileana Cristea

PROVIDER: PXD011845 | Pride | 2019-05-01

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	2016_07_UniProtS_mouse_with_contams.fasta	Fasta
	20180721V_JDF_CHDI_Q140_WB_10M_HDAC4_R1.msf	Msf
	20180721V_JDF_CHDI_Q140_WB_10M_HDAC4_R1.msfView	Msf
	20180721V_JDF_CHDI_Q140_WB_10M_HDAC4_R1_E1.raw	Raw
	20180721V_JDF_CHDI_Q140_WB_10M_HDAC4_R1_E2.raw	Raw

Items per page:

1 - 5 of 367

Publications

Hdac4 Interactions in Huntington's Disease Viewed Through the Prism of Multiomics.

Federspiel Joel D JD Greco Todd M TM Lum Krystal K KK Cristea Ileana M IM

Molecular & cellular proteomics : MCP 20190430 8 suppl 1

Huntington's disease (HD) is a monogenic disorder, driven by the expansion of a trinucleotide (CAG) repeat within the huntingtin (Htt) gene and culminating in neuronal degeneration in the brain, predominantly in the striatum and cortex. Histone deacetylase 4 (Hdac4) was previously found to contribute to the disease progression, providing a potential therapeutic target. Hdac4 knockdown reduced accumulation of misfolded Htt protein and improved HD phenotypes. However, the underlying mechanism rema ...[more]

PMID: 31040226

Similar Datasets

Project description:Huntington's disease (HD) is a dominantly inherited genetic disease caused by mutant huntingtin (htt) protein with expanded polyglutamine tracts. A neuropathological hallmark of HD is the presence of neuronal inclusions of mutant htt. p62 is an important regulatory protein in selective autophagy, a process by which aggregated proteins are degraded, and it is associated with several neurodegenerative disorders including HD. Here we investigated the effect of p62 depletion in three HD model mice: R6/2, HD190QG and HD120QG mice. We found that loss of p62 in these models led to longer lifespans and reduced nuclear inclusions, although cytoplasmic inclusions increased with polyglutamine length. In mouse embryonic fibroblasts (MEFs) with or without p62, mutant htt with a nuclear localization signal (NLS) showed no difference in nuclear inclusion between the two MEF types. In the case of mutant htt without NLS, however, p62 depletion increased cytoplasmic inclusions. Furthermore, to examine the effect of impaired autophagy in HD model mice, we crossed R6/2 mice with Atg5 conditional knockout mice. These mice also showed decreased nuclear inclusions and increased cytoplasmic inclusions, similar to HD mice lacking p62. These data suggest that the genetic ablation of p62 in HD model mice enhances cytoplasmic inclusion formation by interrupting autophagic clearance of polyQ inclusions. This reduces polyQ nuclear influx and paradoxically ameliorates disease phenotypes by decreasing toxic nuclear inclusions. Gene expression profiles were analyzed to examine the effects of p62 depletion in mouse with or without mutant huntingtin exon 1 To examine the effect of p62 depletion on the transcriptome of Huntington's disease model mice, we crossed p62 knockout mice with HD model mice. We extracted total RNA from the striatum of these mice at 8 weeks and used for a microaaray analysis. The samples are HD transgenic mice with p62 knockout (HD_p62KO), HD mice with normal p62 (HD_p62WT), non-HD-transgenic mice with p62 knockout (NT_p62KO), and non-HD-transgenic mice with normal p62 (NT_p62WT).