The Conserved Transcriptional Activation Activity Identified in Dual-Specificity Tyrosine-(Y)-Phosphorylation-Regulated Kinase 1

Abstract

Dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1 (DYRK1) encodes a conserved protein kinase that is indispensable to neuron development. However, whether DYRK1 possesses additional functions apart from kinase function remains poorly understood. In this study, we firstly demonstrated that the C-terminal of ascidian Ciona robusta DYRK1 (CrDYRK1) showed transcriptional activation activity independent of its kinase function. The transcriptional activation activity of CrDYRK1 could be autoinhibited by a repression domain in the N-terminal. More excitingly, both activation and repression domains were retained in HsDYRK1A in humans. The genes, activated by the activation domain of HsDYRK1A, are mainly involved in ion transport and neuroactive ligand–receptor interaction. We further found that numerous mutation sites relevant to the DYRK1A-related intellectual disability syndrome locate in the C-terminal of HsDYRK1A. Then, we identified several specific DNA motifs in the transcriptional regulation region of those activated genes. Taken together, we identified a conserved transcription activation domain in DYRK1 in urochordates and vertebrates. The activation is independent of the kinase activity of DYRK1 and can be repressed by its own N-terminal. Transcriptome and mutation data indicate that the transcriptional activation ability of HsDYRK1A is potentially involved in synaptic transmission and neuronal function related to the intellectual disability syndrome.

Protein-based bioactive coatings: from nanoarchitectonics to applications

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Quantitative Phosphoproteomics Reveals the Requirement of DYRK1-Mediated Phosphorylation of Ion Transport- and Cell Junction-Related Proteins for Notochord Lumenogenesis in Ascidian

“…The dual-specificity tyrosine phosphorylation-regulated protein kinases (DYRKs) are evolutionarily conserved protein kinases, of which DYRK1 is the one that has been most extensively studied. DYRK1 proteins from different species exert their conserved functions by sharing a protein kinase domain and some highly conserved motifs (such as ATP anchor, activation loop, and catalytic loop) [ 1 ]. The ATP anchor is responsible for covering and anchoring the nontransferable phosphates and the adenine ring of ATP.…”