Aven-KO Mouse

AVEN, an apoptosis and caspase activation inhibitor, binds to Bcl-xL and Apaf-1, interfering with Apaf-1-mediated caspase activation and thus functioning as an anti-apoptotic protein [4]. It is involved in multiple pathways, such as DNA damage response, cell-cycle regulation, and translational control of proto-oncogenes [5,6].

In myocardial infarction (MI), down-regulation of AVEN exacerbates cardiac injury. The 3' UTR of AVEN is lengthened after MI, leading to its down-regulation. Knockdown of AVEN increases cardiomyocyte apoptosis, while restoring its expression improves cardiac function [1]. In lung adenocarcinoma (LUAD), high AVEN expression is associated with tumor progression and shorter lifespan. Pathway analysis shows alterations in oncogenic pathways like the cell cycle and VEGFA-VEGFR2 pathway [2]. In osteosarcoma, silencing Aven triggers G2 cell-cycle arrest and abolishes ATR-Chk1 DNA damage response signalling, suggesting Aven's role in chemotherapy resistance [3].

In conclusion, AVEN plays a crucial role in anti-apoptosis, cell-cycle regulation, and is involved in disease processes such as post-MI cardiac injury, LUAD, and osteosarcoma. Functional studies, especially those using loss-of-function models, have revealed its significance in these biological processes and disease conditions, providing potential therapeutic targets for related diseases.

References:

1. Yu, Peng, Song, Shuai, Zhang, Xiaokai, Ni, Ting, Sun, Aijun. 2023. Downregulation of apoptotic repressor AVEN exacerbates cardiac injury after myocardial infarction. In Proceedings of the National Academy of Sciences of the United States of America, 120, e2302482120. doi:10.1073/pnas.2302482120. https://pubmed.ncbi.nlm.nih.gov/37816050/

2. Fan, Dengxia, Yang, Moses, Lee, Hye Jung, Lee, Jeong Hee, Kim, Hong Sook. 2023. AVEN: a novel oncogenic biomarker with prognostic significance and implications of AVEN-associated immunophenotypes in lung adenocarcinoma. In Frontiers in molecular biosciences, 10, 1265359. doi:10.3389/fmolb.2023.1265359. https://pubmed.ncbi.nlm.nih.gov/37908231/

3. Baranski, Zuzanna, Booij, Tijmen H, Cleton-Jansen, Anne-Marie, Hogendoorn, Pancras C W, Danen, Erik H J. 2015. Aven-mediated checkpoint kinase control regulates proliferation and resistance to chemotherapy in conventional osteosarcoma. In The Journal of pathology, 236, 348-59. doi:10.1002/path.4528. https://pubmed.ncbi.nlm.nih.gov/25757065/

4. Chau, B N, Cheng, E H, Kerr, D A, Hardwick, J M. . Aven, a novel inhibitor of caspase activation, binds Bcl-xL and Apaf-1. In Molecular cell, 6, 31-40. doi:. https://pubmed.ncbi.nlm.nih.gov/10949025/

5. Thandapani, Palaniraja, Song, Jingwen, Gandin, Valentina, Topisirovic, Ivan, Richard, Stéphane. 2015. Aven recognition of RNA G-quadruplexes regulates translation of the mixed lineage leukemia protooncogenes. In eLife, 4, . doi:10.7554/eLife.06234. https://pubmed.ncbi.nlm.nih.gov/26267306/

6. Guo, Jessie Yanxiang, Yamada, Ayumi, Kajino, Taisuke, Hardwick, J Marie, Kornbluth, Sally. 2008. Aven-dependent activation of ATM following DNA damage. In Current biology : CB, 18, 933-42. doi:10.1016/j.cub.2008.05.045. https://pubmed.ncbi.nlm.nih.gov/18571408/