Aatf, also known as Apoptosis Antagonizing Transcription Factor or Che-1, is a multifunctional protein that interacts with RNA polymerase II. It is highly conserved in eukaryotes. Aatf functions as a transcriptional co-activator regulating gene expression and plays a dual role in cell cycle regulation by influencing the retinoblastoma-E2F transcription factor (Rb-E2F) complex and the specificity protein 1 (Sp1) transcription factor. It is involved in pathways related to cell proliferation, apoptosis, and survival, and is also crucial for ribosome biosynthesis [1,2].

Aatf has been shown to be overexpressed in several cancers such as hepatocellular carcinoma, bladder cancer, and head and neck squamous cell carcinoma. In hepatocellular carcinoma, inhibiting Aatf disrupts tumor angiogenesis, potentially serving as a treatment approach [3]. In bladder and head and neck squamous cell carcinomas, Aatf overexpression promotes malignant behavior, regulating chemo-sensitivity and apoptosis through proteins like Survivin and the STAT3/Survivin signaling pathway, suggesting it could be a therapeutic target [4,5]. In neurons, over-expressing Aatf reduces infarct volume, alleviates neuronal death, and promotes neurological functions by inhibiting parthanatos [6].

In conclusion, Aatf is a key regulator in various biological processes. Its overexpression in certain cancers and its role in protecting cells from stress stimuli make it an important area of study. The findings from in vivo studies in different disease models, like those in cancer and neuronal ischemia/reperfusion injury, highlight its potential as a biomarker and therapeutic target, contributing to a better understanding of disease mechanisms and potential treatment strategies.

References:

1. Srinivas, Akshatha N, Suresh, Diwakar, Mirshahi, Faridoddin, Sanyal, Arun J, Kumar, Divya P. 2020. Emerging roles of AATF: Checkpoint signaling and beyond. In Journal of cellular physiology, 236, 3383-3395. doi:10.1002/jcp.30141. https://pubmed.ncbi.nlm.nih.gov/33145763/

2. Kaiser, Rainer W J, Erber, Johanna, Höpker, Katja, Fabretti, Francesca, Müller, Roman-Ulrich. 2020. AATF/Che-1-An RNA Binding Protein at the Nexus of DNA Damage Response and Ribosome Biogenesis. In Frontiers in oncology, 10, 919. doi:10.3389/fonc.2020.00919. https://pubmed.ncbi.nlm.nih.gov/32587828/

3. Suresh, Diwakar, Srinivas, Akshatha N, Prashant, Akila, Santhekadur, Prasanna K, Kumar, Divya P. 2023. AATF inhibition exerts antiangiogenic effects against human hepatocellular carcinoma. In Frontiers in oncology, 13, 1130380. doi:10.3389/fonc.2023.1130380. https://pubmed.ncbi.nlm.nih.gov/37361585/

4. Tan, Shutao, Fu, Lin, Dong, Qianze. 2021. AATF is Overexpressed in Human Bladder Cancer and Regulates Chemo-Sensitivity Through Survivin. In OncoTargets and therapy, 14, 5493-5505. doi:10.2147/OTT.S319734. https://pubmed.ncbi.nlm.nih.gov/35002255/

5. Fu, Lin, Jin, Quanxiu, Dong, Qianze, Li, Qingchang. 2021. AATF is Overexpressed in Human Head and Neck Squamous Cell Carcinoma and Regulates STAT3/Survivin Signaling. In OncoTargets and therapy, 14, 5237-5248. doi:10.2147/OTT.S333134. https://pubmed.ncbi.nlm.nih.gov/34785906/

6. Xu, Wei, Hu, Zhen, Yin, Dou, Jin, Wei, Ren, Chuan-Cheng. 2022. AATF Competitively Interacts with Nuclear AIF and Inhibits Parthanatos of Neurons in dMCAO/R and OGD/R Models. In Journal of molecular neuroscience : MN, 72, 2218-2232. doi:10.1007/s12031-022-02064-0. https://pubmed.ncbi.nlm.nih.gov/36058992/