Ajuba transactivates N-cadherin expression in colorectal cancer cells through interaction with Twist

Ajuba 通过与 Twist 相互作用激活结直肠癌细胞中的 N-钙粘蛋白表达

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作者:Zhaoxia Wu, Xiuqun Zou, Ying Xu, Fengli Zhou, Rong Kuai, Ji Li, Daming Yang, Yimin Chu, Haixia Peng

Abstract

Ajuba is a multiple LIM domain-containing protein and functions as a transcriptional coregulator to modulate many gene expressions in various cellular processes. Here, we describe that the LIM domain of Ajuba interacts with Twist, and the Twist box is a pivotal motif for the interaction. Biologically, Ajuba enhances transcription of target gene N-cadherin as an obligate coactivator of Twist. The enhancement is achieved by binding to the E-box element within N-cadherin promoter as revealed by luciferase reporter and chromatin immunoprecipitation assays. Mechanistic investigation demonstrates that Ajuba recruits CBP and Twist to form a ternary complex at the Twist target promoter region and concomitantly enhances histone acetylation at these sites. These findings identify that Twist is a new interacting protein of Ajuba and Ajuba/Twist/CBP ternary complex may be a potential treatment strategy for Twist-related tumour metastasis.

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