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Identification of Kinase-substrate Pairs Using High Throughput Screening
Published on: August 29, 2015
The ATAC acetyltransferase complex coordinates MAP kinases to regulate JNK target genes
Tamaki Suganuma1, Arcady Mushegian, Selene K Swanson
1Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
The ATAC histone acetyltransferase complex acts as a cofactor for c-Jun, regulating gene expression and suppressing upstream signaling during the cellular response to stress.
Area of Science:
- Molecular Biology
- Cell Signaling
- Epigenetics
Background:
- Signal transduction pathways, such as Jun N-terminal kinase (JNK), activate transcription factors like c-Jun to regulate gene expression in response to extracellular stimuli.
- Histone acetyltransferase (HAT) complexes play crucial roles in modulating chromatin structure and influencing gene transcription.
Purpose of the Study:
- To investigate the role of the ATAC (Ada two A containing) histone acetyltransferase complex as a transcriptional cofactor for c-Jun.
- To elucidate the function of ATAC in regulating JNK target genes and its involvement in the cellular stress response.
Main Methods:
- Chromatin immunoprecipitation assays to assess c-Jun occupancy and H4K16 acetylation at target genes.
- Immunofluorescence microscopy to observe the colocalization of ATAC and c-Jun under osmotic stress.
- Biochemical assays to analyze the recruitment of kinases and the suppression of JNK activation.
Main Results:
- ATAC complex is essential for c-Jun binding to Jra and chickadee genes and for H4K16 acetylation.
- ATAC colocalizes with c-Jun during osmotic stress, recruiting upstream kinases (Misshapen, MKK4, JNK) and inhibiting further JNK activation.
- The CG10238 subunit of ATAC is critical for MAPK relocalization and JNK pathway suppression.
Conclusions:
- The ATAC complex functions as a transcriptional coactivator for c-Jun at specific target genes.
- ATAC acts as a negative regulator of upstream MAP kinase signaling, suppressing JNK activation during stress.
- ATAC integrates transcriptional regulation and signal transduction modulation in response to cellular cues.
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