Fggy-KO Mouse

Fggy, or FGGY carbohydrate kinase domain containing, belongs to the FGGY family of carbohydrate kinases. It phosphorylates d -ribulose, and may act as a metabolite repair enzyme, re -phosphorylating free d -ribulose in yeast and mammals [4]. In human cells, it can also participate in ribitol metabolism.

In lung squamous cell carcinoma (LUSC), LINE-1 retrotransposition can disrupt the FGGY gene. Overexpression of the resulting chimeric transcript L1-FGGY or knockdown of FGGY promotes cell proliferation, invasion in vitro, and tumorigenesis in vivo, along with dysregulation of cell energy metabolism and cytokine/chemotaxin transcription. Specific reverse-transcription inhibitors can counter L1-FGGY abundance, inhibit tumor growth, and recover metabolism dysfunction [3]. In colorectal cancer, silencing FGGY inhibits cell viability, induces cell cycle arrest, promotes apoptosis, and enhances senescence-associated β-galactosidase activity by activating the p53/p21 signaling pathway [2]. In skeletal muscle, Fggy is expressed and alternatively spliced, and its ectopic expression inhibits muscle cell differentiation and attenuates the MAP kinase and Akt signaling pathways [1].

In summary, Fggy plays important roles in multiple biological processes and diseases. In LUSC, disruption of FGGY by LINE-1 retrotransposition promotes tumor development, while in colorectal cancer, down-regulating FGGY promotes cell senescence. In skeletal muscle, Fggy affects muscle cell differentiation and signaling pathways. These findings from functional studies, including gene knockdown experiments, help understand the functions of Fggy in disease and normal physiological processes.

References:

1. Smith, Anastasia L, Gjoka, Erisa, Izhar, Mahnoor, De Las Casas, Annabella, Waddell, David S. 2021. FGGY carbohydrate kinase domain containing is expressed and alternatively spliced in skeletal muscle and attenuates MAP kinase and Akt signaling. In Gene, 800, 145836. doi:10.1016/j.gene.2021.145836. https://pubmed.ncbi.nlm.nih.gov/34280510/

2. Liu, Liya, Wu, Meizhu, Chen, Youqin, Shen, Aling, Li, Li. 2025. Downregulating FGGY carbohydrate kinase domain containing promotes cell senescence by activating the p53/p21 signaling pathway in colorectal cancer. In International journal of molecular medicine, 55, . doi:10.3892/ijmm.2025.5522. https://pubmed.ncbi.nlm.nih.gov/40116125/

3. Zhang, Rui, Zhang, Fan, Sun, Zeguo, Zhang, Weijia, Yu, Jinpu. 2019. LINE-1 Retrotransposition Promotes the Development and Progression of Lung Squamous Cell Carcinoma by Disrupting the Tumor-Suppressor Gene FGGY. In Cancer research, 79, 4453-4465. doi:10.1158/0008-5472.CAN-19-0076. https://pubmed.ncbi.nlm.nih.gov/31289132/

4. Singh, Charandeep, Glaab, Enrico, Linster, Carole L. 2016. Molecular Identification of d-Ribulokinase in Budding Yeast and Mammals. In The Journal of biological chemistry, 292, 1005-1028. doi:10.1074/jbc.M116.760744. https://pubmed.ncbi.nlm.nih.gov/27909055/