Reps2-KO Mouse

Reps2, also known as Ral-binding protein 1-associated Eps domain-containing 2 or POB1 (Partner of RalBP1), has emerged as a significant molecule since its discovery in the late 1990s as a signaling molecule in the Ras/Ral pathway. It contains Eps15 homology (EH) domains, proline-rich regions, and a coiled-coil domain, playing a crucial role in receptor-mediated endocytosis and coordinating the internalization of various receptors with molecular signaling [1].

In human lens epithelial cells, down-regulation of REPS2 facilitates FGF-induced adhesion and migration through FAK/Cdc42 signaling, contributing to posterior capsule opacification after cataract surgery [2]. In hepatocellular carcinoma, liver X receptor agonists increase REPS2 expression at the transcriptional level, and the inhibitory effect of these agonists on HCC cell proliferation and migration is related to REPS2 [3]. In prostate cancer, REPS2 expression is down-regulated during progression from androgen-dependent to androgen-independent growth, and overexpression of REPS2 induces apoptosis and inhibits growth factor signaling [4,6]. Also, in breast cancer, REPS2 expression is associated with extended survival times, suggesting it may be a favorable prognostic and predictive biomarker [5]. In esophageal squamous cell carcinoma, down-regulation of REPS2 is associated with malignant progression, and it is an independent prognostic factor [7]. In dopaminergic cells, stable overexpression of REPS2 reduces paraquat toxicity [8].

In conclusion, Reps2 is an important gene involved in receptor-mediated endocytosis and growth factor signaling. Its dysregulation is associated with various diseases such as posterior capsule opacification, hepatocellular carcinoma, prostate cancer, breast cancer, and esophageal squamous cell carcinoma. Studies on Reps2, especially through in vivo models, help us understand its role in these disease processes and may provide potential therapeutic targets.

References:

1. Badway, Joseph A, Baleja, James D. 2011. Reps2: a cellular signaling and molecular trafficking nexus. In The international journal of biochemistry & cell biology, 43, 1660-3. doi:10.1016/j.biocel.2011.08.014. https://pubmed.ncbi.nlm.nih.gov/21907823/

2. Wen, Chan, Wang, Chen, Hu, Conghui, Shao, Yongping, Pei, Cheng. 2022. REPS2 downregulation facilitates FGF-induced adhesion and migration in human lens epithelial cells through FAK/Cdc42 signaling and contributes to posterior capsule opacification. In Cellular signalling, 97, 110378. doi:10.1016/j.cellsig.2022.110378. https://pubmed.ncbi.nlm.nih.gov/35690292/

3. He, Xiao-Yu, Zhu, Meng-Meng, Zheng, Juan, Han, Ji-Hong, Chen, Yuan-Li. 2022. Liver X receptor agonists exert antitumor effects against hepatocellular carcinoma via inducing REPS2 expression. In Acta pharmacologica Sinica, 44, 635-646. doi:10.1038/s41401-022-00961-z. https://pubmed.ncbi.nlm.nih.gov/35995867/

4. Oosterhoff, Josien K, Penninkhof, Fred, Brinkmann, Albert O, Anton Grootegoed, J, Blok, Leen J. . REPS2/POB1 is downregulated during human prostate cancer progression and inhibits growth factor signalling in prostate cancer cells. In Oncogene, 22, 2920-5. doi:. https://pubmed.ncbi.nlm.nih.gov/12771942/

5. Doolan, P, Clynes, M, Kennedy, S, Crown, J, O'Driscoll, L. 2009. TMEM25, REPS2 and Meis 1: favourable prognostic and predictive biomarkers for breast cancer. In Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 30, 200-9. doi:10.1159/000239795. https://pubmed.ncbi.nlm.nih.gov/19776672/

6. Penninkhof, Fred, Grootegoed, J Anton, Blok, Leen J. . Identification of REPS2 as a putative modulator of NF-kappaB activity in prostate cancer cells. In Oncogene, 23, 5607-15. doi:. https://pubmed.ncbi.nlm.nih.gov/15184881/

7. Zhang, Hang, Duan, Chao-Jun, Zhang, Heng, Cheng, Yuan-Da, Zhang, Chun-Fang. . Expression and clinical significance of REPS2 in human esophageal squamous cell carcinoma. In Asian Pacific journal of cancer prevention : APJCP, 14, 2851-7. doi:. https://pubmed.ncbi.nlm.nih.gov/23803043/

8. Rodriguez-Rocha, Humberto, Garcia Garcia, Aracely, Zavala-Flores, Laura, Madayiputhiya, Nandakumar, Franco, Rodrigo. 2012. Glutaredoxin 1 protects dopaminergic cells by increased protein glutathionylation in experimental Parkinson's disease. In Antioxidants & redox signaling, 17, 1676-93. doi:10.1089/ars.2011.4474. https://pubmed.ncbi.nlm.nih.gov/22816731/