期刊
MOLECULAR AND CELLULAR BIOLOGY
卷 22, 期 24, 页码 8409-8414出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.22.24.8409-8414.2002
关键词
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ASC-2, a recently isolated transcriptional coactivator molecule, stimulates transactivation by multiple transcription factors, including nuclear receptors. We generated a potent dominant negative fragment of ASC-2, encompassing the N-terminall LXXLL motif that binds a broad range of nuclear receptors. This fragment, termed DN1, specifically inhibited endogenous ASC-2 from binding these receptors in vivo, whereas DN1/m, in which the LXXLL motif was mutated to LXXAA to abolish the receptor interactions, was inert. Interestingly, DNI transgenic mice but not DN1/m transgenic mice exhibited severe microphthalmia and posterior lenticorms with cataract as well as a variety of pathophysiological phenotypes in many other organs. Our results provide a novel insight into the molecular and histopathological mechanism of posterior lenticorms with cataract and attest to the importance of ASC-2 as a pivotal transcriptional coactivator of nuclear receptors in vivo.
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