Ajuba is a LIM protein with an unstructured proline/glycine-rich preLIM region at the N-terminus and conserved tandem LIM motifs at the C-terminus. It contains both nuclear export and localization sequences, enabling it to shuttle between the cytoplasm and nucleus, and acts as a versatile scaffold in various protein complexes. Ajuba is involved in multiple cellular functions like cell adhesion, motility, mitosis, survival, gene expression, microRNA processing, and mechanical force sensing. It regulates major signaling pathways such as Wnt, RAS/ERK, JAK/STAT, and Hippo, and acts as a co-regulator of key transcription factors, which is of great importance in oncogenesis and various biological processes [1].

Knockout of Ajuba using CRISPR/Cas9 is embryonic lethal in mice. shRNA-mediated targeting of Ajuba in liver cells reduces cell proliferation, delays cell entry into S-phase, reduces cell survival and tumour growth in vivo, and increases the expression of the DNA damage marker γH2AX, indicating its role in liver cell proliferation, DNA replication, and damage repair [4]. In breast cancer, Ajuba overexpression promotes cell growth, invasion, cell cycle progression, and chemoresistance, and is correlated with poor prognosis through the TAZ-GLUT3/Survivin pathway [2]. In colorectal cancer, Ajuba enhances N-cadherin transcription by interacting with Twist, potentially contributing to tumour metastasis [3].

In conclusion, Ajuba is crucial for multiple cellular functions and biological processes. Studies using Ajuba knockout mouse models have revealed its significant roles in diseases such as liver cancer, breast cancer, and colorectal cancer, mainly through its involvement in cell proliferation, DNA-related processes, and regulation of signaling pathways and transcription factors. These findings provide potential therapeutic targets for treating related cancers.

References:

1. Jia, Hao, Peng, Haixia, Hou, Zhaoyuan. 2019. Ajuba: An emerging signal transducer in oncogenesis. In Pharmacological research, 151, 104546. doi:10.1016/j.phrs.2019.104546. https://pubmed.ncbi.nlm.nih.gov/31740385/

2. Li, Xiang, Zhao, Gexin, Mi, Xiaoyi, Li, Xinmin, Liu, Bin. 2022. Ajuba Overexpression Promotes Breast Cancer Chemoresistance and Glucose Uptake through TAZ-GLUT3/Survivin Pathway. In BioMed research international, 2022, 3321409. doi:10.1155/2022/3321409. https://pubmed.ncbi.nlm.nih.gov/35178446/

3. Wu, Zhaoxia, Zou, Xiuqun, Xu, Ying, Chu, Yimin, Peng, Haixia. 2021. Ajuba transactivates N-cadherin expression in colorectal cancer cells through interaction with Twist. In Journal of cellular and molecular medicine, 25, 8006-8014. doi:10.1111/jcmm.16731. https://pubmed.ncbi.nlm.nih.gov/34173718/

4. Dommann, Noëlle, Gavini, Jacopo, Sánchez-Taltavull, Daniel, Candinas, Daniel, Stroka, Deborah. 2022. LIM protein Ajuba promotes liver cell proliferation through its involvement in DNA replication and DNA damage control. In FEBS letters, 596, 1746-1764. doi:10.1002/1873-3468.14371. https://pubmed.ncbi.nlm.nih.gov/35535434/