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 accessibilty and loading of the MCM helicase.[5][6] GRWD1 has also been shown to play a critical role in ribosome biogenesis.[5]

GRWD1
Identifiers
AliasesGRWD1, CDW4, GRWD, RRB1, WDR28, glutamate-rich WD repeat containing 1, glutamate rich WD repeat containing 1
External IDsOMIM: 610597; MGI: 2141989; HomoloGene: 6644; GeneCards: GRWD1; OMA:GRWD1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_031485

NM_153419

RefSeq (protein)

NP_113673

NP_700468

Location (UCSC)Chr 19: 48.45 – 48.46 MbChr 7: 45.47 – 45.48 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Role in cancer

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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

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000105447Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000053801Ensembl, 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. ^ a b 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

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