Interaction with Polyglutamine-expanded Huntingtin Alters Cellular Distribution and RNA Processing of Huntingtin Yeast Two-hybrid Protein A (HYPA)

Jiang, Ya Jun; Xia, Mei; Yuan, Jin Qiao; Xie, Yuan; Yan, Xian Zhong; Hu, Hong Yu

doi:10.1074/jbc.m110.216333

Cited by 27 publications

(38 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A Mutation in the ZnF Domain of Atx7 Disrupts Its Interaction with and Sequestration of USP22-Our previous study indicated that specific interaction is important for the sequestration of its interacting partners by polyQ proteins (33,35). We proposed that the sequestration of USP22 by Atx7 EPQ is also closely associated with their interaction.…”

Section: Polyq-expanded Atx7 Specifically Sequesters Usp22 Intomentioning

confidence: 99%

“…Our previous studies have focused on the neurodegenerative disease-related proteins that sequester their interacting partners into insoluble aggregates or inclusions (11,(32)(33)(34). Recently, we revealed that aggregation of polyQ-expanded ataxin 3 (Atx3) specifically sequesters ubiquitin chains and P97/ VCP into inclusions and impairs the normal function of P97/ VCP (35).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Aggregation of Polyglutamine-expanded Ataxin 7 Protein Specifically Sequesters Ubiquitin-specific Protease 22 and Deteriorates Its Deubiquitinating Function in the Spt-Ada-Gcn5-Acetyltransferase (SAGA) Complex

Liu

et al. 2015

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Background: Expansion of the polyQ tract in ataxin 7 is the main pathology of SCA7. Results: The aggregates formed by polyQ-expanded ataxin 7 sequester USP22 through specific interactions. Conclusion: Sequestration of USP22 impairs its deubiquitinating function in the SAGA complex. Significance: This provides evidence for the hijacking model in which specific sequestration leads to cytotoxicity and neurodegeneration.

show abstract

Section: Polyq-expanded Atx7 Specifically Sequesters Usp22 Intomentioning

confidence: 99%

mentioning

confidence: 99%

Aggregation of Polyglutamine-expanded Ataxin 7 Protein Specifically Sequesters Ubiquitin-specific Protease 22 and Deteriorates Its Deubiquitinating Function in the Spt-Ada-Gcn5-Acetyltransferase (SAGA) Complex

Liu

et al. 2015

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…There are many literatures reporting that polyQ expansion is responsible for enhancing the interaction with the partners and sequestration of them916. To clarify whether polyQ tract has notable effect on the interactions with its partners, we measured the binding affinities of these three Atx3-IIC forms with K48-diUb or P97 by isothermal titration calorimetry (ITC) experiments.…”

Section: Resultsmentioning

confidence: 99%

“…A hypothesis states that formation of inclusions is one of the cellular protective processes to resist the toxicities of the soluble oligomers of the misfolded disease proteins78. However, there are some studies suggesting that the insoluble aggregates or inclusions are able to sequester normal cellular proteins into the inclusions and cause dysfunction of these essential proteins910111213141516. These experimental data support an assumption that more and more cellular proteins are sequestered into insoluble aggregates or inclusions that cause them dysfunctional and cytotoxic.…”

mentioning

confidence: 89%

Aggregation of polyglutamine-expanded ataxin-3 sequesters its specific interacting partners into inclusions: Implication in a loss-of-function pathology

Liu

et al. 2014

Sci Rep

Self Cite

114

View full text Add to dashboard Cite

Expansion of polyglutamine (polyQ) tract may cause protein misfolding and aggregation that lead to cytotoxicity and neurodegeneration, but the underlying mechanism remains to be elucidated. We applied ataxin-3 (Atx3), a polyQ tract-containing protein, as a model to study sequestration of normal cellular proteins. We found that the aggregates formed by polyQ-expanded Atx3 sequester its interacting partners, such as P97/VCP and ubiquitin conjugates, into the protein inclusions through specific interactions both in vitro and in cells. Moreover, this specific sequestration impairs the normal cellular function of P97 in down-regulating neddylation. However, expansion of polyQ tract in Atx3 does not alter the conformation of its surrounding regions and the interaction affinities with the interacting partners, although it indeed facilitates misfolding and aggregation of the Atx3 protein. Thus, we propose a loss-of-function pathology for polyQ diseases that sequestration of the cellular essential proteins via specific interactions into inclusions by the polyQ aggregates causes dysfunction of the corresponding proteins, and consequently leads to neurodegeneration.

show abstract

“…Numerous proteins can be sequestered by the nuclear inclusions, so that their functions must be abolished, which can also be recognized as a pathogen for the polyQ diseases. Our previous work has shown that polyQ expanded huntingtin (Htt) can sequester Htt two-hybrid protein A (HYPA) through its PRR interaction, and thus impairs the function of HYPA in pre-mRNA splicing [32]. It is quite possible to be a similar case in R85FL.…”

Section: Discussionmentioning

confidence: 97%

Structural basis for recognition of the third SH3 domain of full‐length R85 (R85FL)/ponsin by ataxin‐7

Jiang

Zhou

et al. 2013

FEBS Letters

Self Cite

View full text Add to dashboard Cite

Edited by Berend WieringaKeywords: Ataxin-7 Proline-rich region R85FL/ponsin SH3 domain Polyglutamine Inclusion body a b s t r a c t Ataxin-7 (Atx7) is a component of the nuclear transcription co-activator complex; its polyglutamine (polyQ) expansion may cause nuclear accumulation and recruit numerous proteins to the intranuclear inclusion bodies. Full-length R85 (R85FL) is such a protein sequestered by polyQ-expanded Atx7. Here, we report that Atx7 specifically interacts with the third SH3 domain (SH3C) of R85FL through its second portion of proline-rich region (PRR). NMR structural analysis of the SH3C domain and its complex with PRR revealed that SH3C contains a large negatively charged surface for binding with the RRTR motif of Atx7. Microscopy imaging demonstrated that sequestration of R85FL by the polyQ-expanded Atx7 in cell is mediated by this specific SH3C-PRR interaction, which is implicated in the pathogenesis of spinocerebellar ataxia 7. Structured summary of protein interactions:Atx7 PP2 and SH3C bind by isothermal titration calorimetry (View Interaction: 1,2,3,4,5,6,7,8,9,10,11,12) Atx7 binds to SH3C by pull down (View interaction) Atx7 100Q and SH3C colocalize by fluorescence microscopy (View interaction) SH3C and Atx7 bind by nuclear magnetic resonance (View interaction)

show abstract

Interaction with Polyglutamine-expanded Huntingtin Alters Cellular Distribution and RNA Processing of Huntingtin Yeast Two-hybrid Protein A (HYPA)

Cited by 27 publications

References 51 publications

Aggregation of Polyglutamine-expanded Ataxin 7 Protein Specifically Sequesters Ubiquitin-specific Protease 22 and Deteriorates Its Deubiquitinating Function in the Spt-Ada-Gcn5-Acetyltransferase (SAGA) Complex

Aggregation of Polyglutamine-expanded Ataxin 7 Protein Specifically Sequesters Ubiquitin-specific Protease 22 and Deteriorates Its Deubiquitinating Function in the Spt-Ada-Gcn5-Acetyltransferase (SAGA) Complex

Aggregation of polyglutamine-expanded ataxin-3 sequesters its specific interacting partners into inclusions: Implication in a loss-of-function pathology

Structural basis for recognition of the third SH3 domain of full‐length R85 (R85FL)/ponsin by ataxin‐7

Contact Info

Product

Resources

About