A screen for modulators of N-end rule pathway

dc.contributor.authorDasgupta, Rinki
dc.contributor.authorKasu, Yasar
dc.contributor.authorBrower, Christopher
dc.date.accessioned2019-04-29T17:29:06Z
dc.date.available2019-04-29T17:29:06Z
dc.date.issued2019
dc.descriptionCreative Arts and Research Symposiumen_US
dc.description.abstractArginyl‐tRNA‐protein transferase (ATE1) is responsible for the posttranslational transfer of arginine onto proteins bearing N‐terminal acidic amino acids. The N‐end rule pathway of the ubiquitin proteasome system recognizes proteins bearing N‐terminal hydrophobic or basic amino acids such as arginine. These Nterminal amino acids function as degradation signals called Ndegrons. We discovered that ATE1 is required for the degradation of TDP43247, a specific fragment of the human TDP43 protein associated with Amyotrophic Lateral Sclerosis and other forms of dementia. Here, we generated a fluorescent GFP reporter bearing the N‐degron of TDP43247 (247‐ DLIIKGISVHISNAEPK‐263) which elicits a “digital response” with respect to degradation by the N‐ end rule pathway. Using this reporter, we are developing a highly sensitive, cell‐based screen to identify chemical or genetic modifiers of the N‐end rule pathway. Ultimately, this work may offer therapeutic potential in treating neurodegeneration.en_US
dc.description.sponsorshipFaculty Sponsor: Dr. Christopher Broweren_US
dc.identifier.urihttps://hdl.handle.net/11274/11256
dc.language.isoen_USen_US
dc.titleA screen for modulators of N-end rule pathwayen_US
dc.typePosteren_US

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