10 research outputs found

    The AIB1/NCOA3/SRC-3 Oncogene

    Get PDF
    A member of the NCOA/SRC/p160 co-activator family, AIB1 is amplified and overexpressed in multiple cancer types, notably breast, ovarian, and pancreatic cancer. Common to all members of the NCOA/SRC/p160 family are bHLH-PAS, receptor interaction, and CBP/p300 interacting activation domains. The protein acts as a scaffold to support the transcriptional activity of many DNA binding transcription factors, such as the ER, AP-1, E2F, NFκB, and TEADs. In doing so, the multi-domain protein facilitates chromatin remodeling and oncogenic gene transcription. Further, the AIB1Δ4 isoform promotes tumorigenesis and metastasis through interaction with chromatin in the nucleus or at the periphery of the cell. Pathologically, AIB1 promotes the transformation of normal tissue to cancerous lesions in multiple diseases, and loss delays progression. AIB1 has also been implicated in cancer recurrence and pharmacological resistance. We will discuss the structure and isoforms of AIB1, the physiological consequences of its interaction with transcription factors and hormone receptors, and clinical significance of the protein

    Unique genetic responses revealed in RNA-seq of the spleen of chickens stimulated with lipopolysaccharide and short-term heat

    Get PDF
    <div><p>Climate change and disease have large negative impacts on poultry production, but little is known about the interactions of responses to these stressors in chickens. Fayoumi (heat and disease resistant) and broiler (heat and disease susceptible) chicken lines were stimulated at 22 days of age, using a 2x2x2 factorial design including: breed (Fayoumi or broiler), inflammatory stimulus (lipopolysaccharide (LPS) or saline), and temperature (35°C or 25°C). Transcriptional changes in spleens were analyzed using RNA-sequencing on the Illumina HiSeq 2500. Thirty-two individual cDNA libraries were sequenced (four per treatment) and an average of 22 million reads were generated per library. Stimulation with LPS induced more differentially expressed genes (DEG, log<sub>2</sub> fold change ≥ 2 and FDR ≤ 0.05) in the broiler (N = 283) than the Fayoumi (N = 85), whereas heat treatment resulted in fewer DEG in broiler (N = 22) compared to Fayoumi (N = 107). The double stimulus of LPS+heat induced the largest numbers of changes in gene expression, for which broiler had 567 DEG and Fayoumi had 1471 DEG of which 399 were shared between breeds. Further analysis of DEG revealed pathways impacted by these stressors such as Remodelling of Epithelial Adherens Junctions due to heat stress, Granulocyte Adhesion and Diapedesis due to LPS, and Hepatic Fibrosis/Hepatic Stellate Cell Activation due to LPS+heat. The genes and pathways identified provide deeper understanding of the response to the applied stressors and may serve as biomarkers for genetic selection for heat and disease tolerant chickens.</p></div
    corecore