TWIST1의 결합 단백질 SKP2의 동정 및 상호작용 연구

Abstract

Twist1 is a basic helix-loop-helix (bHLH) type transcription factor, originally identified in early mesodermal patterning in Drosophila. Twist homozygous null mutant embryos are not viable in mice and heterozygous loss of Twist results in the autosomal dominant Saethre-Chotzen syndrome in human. Epithelial to mesenchymal transition (EMT) has been recognized as a crucial process during embryonic development. In progression of carcinoma, EMT also plays an essential role. Twist plays an important role in programmed cell death and cancer metastasis. Overexpression of Twist causes an epithelial to mesenchymal transition (EMT) both in mouse and human cancer cell lines. In human breast cancers, upregulated expression of Twist is correlated with a highly invasive lobular carcinoma. In spite of the significance in developmental biology and tumor metastasis, little is known about regulatory mechanism of Twist. In present study, I have demonstrated SKP2 SCF ubiquitin ligase as a novel interacting protein of TWIST1. As an F-box protein, SKP2 recognizes substrate in phosphorylation dependent manner and processes its target by ubiquitin proteasome dependent degradation. However, in this study, the protein stability of TWIST1 was not controlled by SKP2 significantly. Consequently, the biological significance between TWIST1 and SKP2 is remained to be investigated.