Fbxo34-KO Mouse

Fbxo34, an F-box protein, is a component of the Skp1-Cullin-F-box (SCF) complex, which is an important E3 ubiquitin ligase in the ubiquitin proteasome system (UPS) that regulates protein degradation [2]. It is involved in multiple biological processes and has potential significance in various disease conditions.

In the context of HIV-1 latency, overexpression of FBXO34 can activate latent HIV-1 in multiple latent cell lines. It promotes the ubiquitination and degradation of hnRNP U, disrupting the interaction between hnRNP U and HIV-1 mRNA, which is involved in maintaining HIV-1 latency [1]. In oocyte meiotic maturation, depletion of FBXO34 leads to failure of oocyte meiotic resumption due to low MPF activity, while overexpression promotes germinal vesicle breakdown (GVBD) but causes spindle assembly checkpoint (SAC) activation and MI arrest, indicating its role in regulating the G2/M transition and anaphase entry in meiotic oocytes [2]. Also, exome-wide and genome-wide association studies have linked FBXO34 genetic variants with the severity of COVID-19 in patients of European and other ancestries [3,4].

In summary, Fbxo34 plays crucial roles in diverse biological processes such as viral latency, oocyte maturation, and potentially in the severity of COVID-19. Functional studies, including those with possible gene knockout models in the related research, have revealed its significance in these disease-relevant or physiological processes, providing insights into the underlying molecular mechanisms and potential therapeutic targets.

References:

1. Yang, Xinyi, Zhao, Xiaying, Zhu, Yuqi, Lu, Hongzhou, Zhu, Huanzhang. . FBXO34 promotes latent HIV-1 activation by post-transcriptional modulation. In Emerging microbes & infections, 11, 2785-2799. doi:10.1080/22221751.2022.2140605. https://pubmed.ncbi.nlm.nih.gov/36285453/

2. Zhao, Bing-Wang, Sun, Si-Min, Xu, Ke, Sun, Qing-Yuan, Wang, Zhen-Bo. 2021. FBXO34 Regulates the G2/M Transition and Anaphase Entry in Meiotic Oocytes. In Frontiers in cell and developmental biology, 9, 647103. doi:10.3389/fcell.2021.647103. https://pubmed.ncbi.nlm.nih.gov/33842473/

3. Upadhyai, Priyanka, Shenoy, Pooja U, Banjan, Bhavya, Manzoor, Irfan, Das, Ranajit. 2022. Exome-Wide Association Study Reveals Host Genetic Variants Likely Associated with the Severity of COVID-19 in Patients of European Ancestry. In Life (Basel, Switzerland), 12, . doi:10.3390/life12091300. https://pubmed.ncbi.nlm.nih.gov/36143338/

4. Mousa, Mira, Vurivi, Hema, Kannout, Hussein, Tay, Guan K, Alsafar, Habiba S. 2021. Genome-wide association study of hospitalized COVID-19 patients in the United Arab Emirates. In EBioMedicine, 74, 103695. doi:10.1016/j.ebiom.2021.103695. https://pubmed.ncbi.nlm.nih.gov/34775353/