| First Author | Kim SW | Year | 2002 |
| Journal | Mol Cell Biol | Volume | 22 |
| Issue | 24 | Pages | 8409-14 |
| PubMed ID | 12446761 | Mgi Jnum | J:80609 |
| Mgi Id | MGI:2446405 | Doi | 10.1128/MCB.22.24.8409-8414.2002 |
| Citation | Kim SW, et al. (2002) Multiple developmental defects derived from impaired recruitment of ASC-2 to nuclear receptors in mice: implication for posterior lenticonus with cataract. Mol Cell Biol 22(24):8409-14 |
| abstractText | 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-terminal 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, DN1 transgenic mice but not DN1/m transgenic mice exhibited severe microphthalmia and posterior lenticonus 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 lenticonus with cataract and attest to the importance of ASC-2 as a pivotal transcriptional coactivator of nuclear receptors in vivo. |
