Pdap1-KO Mouse

Pdap1, also known as PDGFA-associated protein 1, has diverse functions. It acts as an RNA-binding protein [1]. Pdap1 is involved in multiple biological pathways such as those related to cell proliferation, immune cell regulation, and stress-related responses [2-4, 6, 9]. In the immune system, it is part of a regulatory axis with RFX factors and miR-150 that restrains T-cell proliferation [1]. It also regulates endoplasmic reticulum stress responses related to hepatovirus translation [3].

In Pdap1 conditional knockout mice, depletion of Pdap1 in intestinal epithelial cells impaired mucosal restitution in colitis and inhibited tumor initiation and growth in colitis-associated cancers. Mechanistically, c-Myc directly transactivated Pdap1, which then interacted with EGFR and facilitated EGFR-MAPK-FRA-1 signaling activation to promote CRC progression [2]. In another study, Pdap1 deficiency in mature B cells led to sustained ISR effector expression, increased cell death, and defective AID expression, reducing germinal center B cell formation and impairing antibody gene diversification [4].

In conclusion, Pdap1 is crucial for regulating cell-related processes such as proliferation, survival, and immune-related functions. The Pdap1 conditional knockout mouse models have revealed its significant roles in colorectal cancer and in the regulation of B-cell-mediated humoral immunity, providing insights into the mechanisms of these disease-related biological processes [2,4].

References:

1. Chirichella, Michele, Bianchi, Niccolò, Džafo, Emina, Natoli, Gioacchino, Monticelli, Silvia. 2022. RFX transcription factors control a miR-150/PDAP1 axis that restrains the proliferation of human T cells. In PLoS biology, 20, e3001538. doi:10.1371/journal.pbio.3001538. https://pubmed.ncbi.nlm.nih.gov/35143476/

2. Cui, Hong-Yong, Wei, Wei, Qian, Mei-Rui, Wang, Shi-Jie, Chen, Zhi-Nan. 2022. PDGFA-associated protein 1 is a novel target of c-Myc and contributes to colorectal cancer initiation and progression. In Cancer communications (London, England), 42, 750-767. doi:10.1002/cac2.12322. https://pubmed.ncbi.nlm.nih.gov/35716012/

3. Shirasaki, Takayoshi, Lenarcic, Erik, Misumi, Ichiro, Moorman, Nathaniel J, Lemon, Stanley M. 2024. Hepatovirus translation requires PDGFA-associated protein 1, an eIF4E-binding protein regulating endoplasmic reticulum stress responses. In Science advances, 10, eadq6342. doi:10.1126/sciadv.adq6342. https://pubmed.ncbi.nlm.nih.gov/39565848/

4. Delgado-Benito, Verónica, Berruezo-Llacuna, Maria, Altwasser, Robert, Akalin, Altuna, Di Virgilio, Michela. . PDGFA-associated protein 1 protects mature B lymphocytes from stress-induced cell death and promotes antibody gene diversification. In The Journal of experimental medicine, 217, . doi:10.1084/jem.20200137. https://pubmed.ncbi.nlm.nih.gov/32609329/