Glutamate-rich WD repeat-containing protein 1 is a WD40 repeatprotein (containing five WD40 repeat motifs) that in humans is encoded by the GRWD1gene. It localizes to the nucleus and has known functions in regulating chromatin accessibilty and loading of the MCM helicase.[5][6] GRWD1 has also been shown to play a critical role in ribosome biogenesis.[5]
While some ribosomal proteins like RPL5 and RPL11 are suggested to act as tumor suppressors by inhibiting E3 ubiquitin-protein ligase MDM2 and thus activating p53, others, such as GRWD1, may promote tumorigenesis. Overexpression of GRWD1 suppresses p53 and transforms normal cells, possibly through its interaction with RPL11, preventing it from regulating MDM2.[7]
In addition to its interaction with RPL11, GRWD1 directly interacts with wild-type p53, suppressing its transcriptional activity.[8] Furthermore, overexpression of GRWD1 has been linked to the activation of oncogenic signaling pathways, such as the Notch signaling pathway, through the upregulation of ADAM17.[9]
^Ichikawa MK, Saitoh M (May 2022). "Direct and indirect roles of GRWD1 in the inactivation of p53 in cancer". Journal of Biochemistry. 171 (6): 601–603. doi:10.1093/jb/mvac010. PMID35171268.
^Ding H, Feng Z, Hu K (March 2024). "GRWD1 Over-Expression Promotes Gastric Cancer Progression by Activating Notch Signaling Pathway via Up-Regulation of ADAM17". Digestive Diseases and Sciences. 69 (3): 821–834. doi:10.1007/s10620-023-08208-5. PMID38172445.
Nagase T, Kikuno R, Ohara O (December 2001). "Prediction of the coding sequences of unidentified human genes. XXII. The complete sequences of 50 new cDNA clones which code for large proteins". DNA Research. 8 (6): 319–327. doi:10.1093/dnares/8.6.319. PMID11853319.
Trzcińska AM, Girstun A, Piekiełko A, Kowalska-Loth B, Staroń K (December 2002). "Potential protein partners for the N-terminal domain of human topoisomerase I revealed by phage display". Molecular Biology Reports. 29 (4): 347–352. doi:10.1023/A:1021237021338. PMID12549820. S2CID9602116.
Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, et al. (February 2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nature Cell Biology. 6 (2): 97–105. doi:10.1038/ncb1086. PMID14743216. S2CID11683986.
