Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: ATXN2 is a target of N-terminal proteolysis Spinocerebellar ataxia 2 (SCA2) is a neurodegenerative disorder caused by the expansion of the poly-glutamine (polyQ) tract of Ataxin-2 (ATXN2). Other polyQ-containing proteins such as ATXN7 and huntingtin are associated with the development of neurodegenerative diseases when their N-terminal polyQ domains are expanded. Furthermore, they undergo proteolytic processing events that produce N-terminal fragments that include the polyQ stretch, which are implicated in pathogenesis. Interestingly, N-terminal ATXN2 fragments were reported in a brain extract from a SCA2 patient, but it is currently unknown whether an expanded polyQ domain contributes to ATXN2 proteolytic susceptibility. Here, we used transient expression in HEK293 cells to determine whether ATXN2 is a target for specific N-terminal proteolysis. We found that ATXN2 proteins with either normal or expanded polyQ stretches undergo proteolytic cleavage releasing an N-terminal polyQ-containing fragment. We identified a short amino acid sequence downstream of the polyQ domain that is necessary for N-terminal cleavage of full-length ATXN2 and sufficient to induce proteolysis of a heterologous protein. However, this sequence is not required for cleavage of a short ATXN2 isoform produced from an alternative start codon located just upstream of the CAG repeats encoding the polyQ domain. Our study extends our understanding of ATXN2 posttranslational regulation by revealing that this protein can be the target of specific proteolytic cleavage events releasing polyQ-containing products that are modulated by the N-terminal domain of ATXN2. N-terminal ATXN2 proteolysis of expanded polyQ domains might contribute to SCA2 pathology, as observed in other neurodegenerative disorders caused by polyQ domain expansion.
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The categories of this paper are: biochemistry
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The categories of this paper are: synthetic
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The categories of this paper are: education
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The categories of this paper are: ecology
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The categories of this paper are: physiology
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The categories of this paper are: immunology
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The categories of this paper are: genetics
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The categories of this paper are: bioinformatics
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The categories of this paper are: pathology
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The categories of this paper are: cell
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The categories of this paper are: bioengineering
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The categories of this paper are: and
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The categories of this paper are: epidemiology
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The categories of this paper are: communication
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The categories of this paper are: genomics
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The categories of this paper are: plant