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

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.

Automated summary

Ajuba is a transcriptional coregulator that interacts with Twist to modulate gene expression, particularly enhancing the transcription of the N-cadherin gene. This enhancement is achieved through the formation of a Ajuba/Twist/CBP ternary complex and the enhancement of histone acetylation at target sites.