Multiple developmental defects derived from impaired recruitment of ASC-2 to nuclear receptors in mice: Implication for posterior lenticonus with cataract

Seung Whan Kim, Cheolho Cheong, Young Chang Sohn, Young Hwa Goo, Wan Je Oh, Jung Hwan Park, So Young Joe, Hyen Sam Kang, Duk Kyung Kim, Changwon Kee, Jae Woon Lee, Han Woong Lee

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)8409-8414
Number of pages6
JournalMolecular and cellular biology
Volume22
Issue number24
DOIs
Publication statusPublished - 2002 Dec

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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