Ankrd13a-KO Mouse

Ankrd13a, short for ankyrin repeat domain 13a, is involved in multiple biological processes. It has a role in TNF signaling, where it sets a higher signal threshold for TNF's cytotoxic potential, acting as a gatekeeper of the early cell-death checkpoint [1]. It also appears to be associated with processes like mitophagy in relation to coronary in-stent restenosis, and may play a part in immune and inflammatory responses in this context [5].

ANKRD13a deficiency turns the TNF response from survival to death by promoting the formation of death-inducing complex-II without affecting NF-κB activation. It binds to ubiquitinated-RIP1 via its UIM, limiting the association of FADD and caspase-8 with RIP1 [1]. In acute myeloid leukemia, lncRNA USP30-AS1 may promote cell survival by cis-regulating ANKRD13A, and ANKRD13A might contribute to immune escape by inducing HLA-I internalization [2]. In breast cancer, CYYR1 can direct polyubiquitinated WWP1 toward lysosomal degradation through binding to ANKRD13A, with CYYR1 having tumor-suppressor properties [3]. In medaka fish, miR-204 promotes mesenchymal neural crest and lens cell migration by directly targeting Ankrd13A, which controls focal cell adhesion formation and distribution [4].

In summary, Ankrd13a has essential functions in cell-death regulation, immune-related processes, and cell migration. Studies involving its deficiency or related gene-regulatory mechanisms in models like cell lines and medaka fish have provided insights into its role in diseases such as cancer and in-stent restenosis, highlighting its significance in understanding disease mechanisms and potentially developing treatment strategies.

References:

1. Won, Minho, Park, Kyeong Ah, Kim, Sup, Kim, Jin Man, Hur, Gang Min. 2021. ANKRD13a controls early cell-death checkpoint by interacting with RIP1 independent of NF-κB. In Cell death and differentiation, 29, 1152-1163. doi:10.1038/s41418-021-00906-9. https://pubmed.ncbi.nlm.nih.gov/34839354/

2. Zhou, Wei, Xu, Shilin, Deng, Tingfen, Zhou, Ruiqing, Wang, Caixia. 2021. LncRNA USP30-AS1 promotes the survival of acute myeloid leukemia cells by cis-regulating USP30 and ANKRD13A. In Human cell, 35, 360-378. doi:10.1007/s13577-021-00636-7. https://pubmed.ncbi.nlm.nih.gov/34694569/

3. Perron, Tiphaine, Boissan, Mathieu, Bièche, Ivan, Levy, Laurence, Prunier, Céline. 2024. CYYR1 promotes the degradation of the E3 ubiquitin ligase WWP1 and is associated with favorable prognosis in breast cancer. In The Journal of biological chemistry, 300, 107601. doi:10.1016/j.jbc.2024.107601. https://pubmed.ncbi.nlm.nih.gov/39059493/

4. Avellino, Raffaella, Carrella, Sabrina, Pirozzi, Marinella, Banfi, Sandro, Conte, Ivan. 2013. miR-204 targeting of Ankrd13A controls both mesenchymal neural crest and lens cell migration. In PloS one, 8, e61099. doi:10.1371/journal.pone.0061099. https://pubmed.ncbi.nlm.nih.gov/23620728/

5. Shen, Ming, Chen, Meixian, Chen, Yu, Yu, Yunhua. 2024. Mitophagy related diagnostic biomarkers for coronary in-stent restenosis identified using machine learning and bioinformatics. In Scientific reports, 14, 24137. doi:10.1038/s41598-024-74862-y. https://pubmed.ncbi.nlm.nih.gov/39406802/