GRWD1

GRWD1
Identifiers
Aliases	GRWD1 , CDW4, GRWD, RRB1, WDR28, glutamate-rich WD repeat containing 1, glutamate rich WD repeat containing 1
External IDs	OMIM: 610597; MGI: 2141989; HomoloGene: 6644; GeneCards: GRWD1; OMA:GRWD1 - orthologs
Gene location (Human) Chr. Chromosome 19 (human) [1] Band 19q13.33 Start 48,445,841 bp [1] End 48,457,022 bp [1]
Gene location (Mouse) Chr. Chromosome 7 (mouse) [2] Band 7|7 B3 Start 45,474,647 bp [2] End 45,480,368 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in gastrocnemius muscle stromal cell of endometrium olfactory bulb gonad muscle of thigh mucosa of esophagus left uterine tube skin of leg apex of heart granulocyte Top expressed in internal carotid artery external carotid artery yolk sac epiblast condyle primitive streak fossa somite endothelial cell of lymphatic vessel embryo More reference expression data BioGPS More reference expression data
Gene ontology Molecular function chromatin binding DNA replication origin binding RNA binding protein binding histone binding Cellular component nucleus nucleolus cytosol chromosome protein-containing complex Biological process nucleosome assembly nucleosome disassembly DNA replication Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 83743 101612 Ensembl ENSG00000105447 ENSMUSG00000053801 UniProt Q9BQ67 Q810D6 RefSeq (mRNA) NM_031485 NM_153419 RefSeq (protein) NP_113673 NP_700468 Location (UCSC) Chr 19: 48.45 – 48.46 Mb Chr 7: 45.47 – 45.48 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Glutamate-rich WD repeat-containing protein 1 is a WD40 repeat protein (containing five WD40 repeat motifs) that in humans is encoded by the GRWD1 gene. It localizes to the nucleus and has known functions in regulating chromatin accessibility and loading of the MCM helicase. ^{[5] [6]} GRWD1 has also been shown to play a critical role in ribosome biogenesis. ^[5]

Role in cancer

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]

References

1. GRCh38: Ensembl release 89: ENSG00000105447 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000053801 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Gratenstein K, Heggestad AD, Fortun J, Notterpek L, Pestov DG, Fletcher BS (June 2005). "The WD-repeat protein GRWD1: potential roles in myeloid differentiation and ribosome biogenesis". Genomics. 85 (6): 762–773. doi:10.1016/j.ygeno.2005.02.010. PMID   15885502.
6. "Entrez Gene: GRWD1 glutamate-rich WD repeat containing 1".
7. Takafuji T, Kayama K, Sugimoto N, Fujita M (August 2017). "GRWD1, a new player among oncogenesis-related ribosomal/nucleolar proteins". Cell Cycle. 16 (15): 1397–1403. doi:10.1080/15384101.2017.1338987. PMC   5553401 . PMID   28722511.
8. 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. PMID   35171268.
9. 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. PMID   38172445.

Further reading

• 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 . PMID   11853319.
• Scherl A, Couté Y, Déon C, Callé A, Kindbeiter K, Sanchez JC, et al. (November 2002). "Functional proteomic analysis of human nucleolus". Molecular Biology of the Cell. 13 (11): 4100–4109. doi:10.1091/mbc.E02-05-0271. PMC   133617 . PMID   12429849.
• 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. PMID   12549820. S2CID   9602116.
• 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. PMID   14743216. S2CID   11683986.
• Andersen JS, Lam YW, Leung AK, Ong SE, Lyon CE, Lamond AI, et al. (January 2005). "Nucleolar proteome dynamics". Nature. 433 (7021): 77–83. Bibcode:2005Natur.433...77A. doi:10.1038/nature03207. PMID   15635413. S2CID   4344740.
• Higa LA, Wu M, Ye T, Kobayashi R, Sun H, Zhang H (November 2006). "CUL4-DDB1 ubiquitin ligase interacts with multiple WD40-repeat proteins and regulates histone methylation". Nature Cell Biology. 8 (11): 1277–1283. doi:10.1038/ncb1490. hdl: 10397/34293 . PMID   17041588. S2CID   22180568.
• Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, et al. (November 2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–648. doi: 10.1016/j.cell.2006.09.026 . PMID   17081983. S2CID   7827573.