Breaking Down Autism: DYRK1A Reduces Transcriptional Activity of Neurocritical NOTCH 1 Proteins with HES 5 Promotion

Faculty Mentor Information

Dr. Allan Albig (Mentor), Boise State University

Abstract

It has been previously shown that dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) affects the transcriptional ability of the NOTCH 1 protein in the NOTCH cell signaling pathway. Previous research has failed to examine the effects of DYRK1A on the other three currently identified NOTCH proteins, NOTCH 2, NOTCH 3, and NOTCH 4. We sought to examine if DYRK1A would impact the transcriptional activity of these other three NOTCH proteins using three different promoters that have been previously mentioned in NOTCH1 and DYRK1A articles, including HES 1, HES 5, and 4x CSL. Using luciferase assay analysis with bacterial plasmid transfected 293T cells, we generated inconclusive results for the transcriptional activity of NOTCH 2, NOTCH 3, and NOTCH 4 under all promoter conditions. We further demonstrated that NOTCH 1 expression was attenuated by DYRK1A in all promoter conditions but displayed the most dramatic reduction in expression with HES 5 promotion. This research reinforces existing findings about the impacts of DYRK1A on NOTCH1 transcriptional activity.

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Breaking Down Autism: DYRK1A Reduces Transcriptional Activity of Neurocritical NOTCH 1 Proteins with HES 5 Promotion

It has been previously shown that dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) affects the transcriptional ability of the NOTCH 1 protein in the NOTCH cell signaling pathway. Previous research has failed to examine the effects of DYRK1A on the other three currently identified NOTCH proteins, NOTCH 2, NOTCH 3, and NOTCH 4. We sought to examine if DYRK1A would impact the transcriptional activity of these other three NOTCH proteins using three different promoters that have been previously mentioned in NOTCH1 and DYRK1A articles, including HES 1, HES 5, and 4x CSL. Using luciferase assay analysis with bacterial plasmid transfected 293T cells, we generated inconclusive results for the transcriptional activity of NOTCH 2, NOTCH 3, and NOTCH 4 under all promoter conditions. We further demonstrated that NOTCH 1 expression was attenuated by DYRK1A in all promoter conditions but displayed the most dramatic reduction in expression with HES 5 promotion. This research reinforces existing findings about the impacts of DYRK1A on NOTCH1 transcriptional activity.