Glutamate-rich WD repeat-containing protein 1 (GRWD1)

Glutamate-rich WD repeat-containing protein 1 (GRWD1) is a nuclear protein characterized by a glutamate-rich domain and WD40 repeats. It acts primarily as a histone chaperone, binding to chromatin and regulating chromatin accessibility at DNA replication origins, facilitating proper loading of the MCM helicase and thereby ensuring DNA replication licensing and genome integrity[1][2][3][4]. GRWD1 also participates in ribosome biogenesis and has diverse interactions with proteins involved in transcription, translation, and chromatin organization[2][4]. Functionally, GRWD1 modulates the tumor suppressor p53 pathway by interacting with ribosomal proteins such as RPL11 and RPL23, antagonizing their regulatory effects on p53 via MDM2, leading to decreased p53 activity and promoting tumorigenesis[2][3][4]. Overexpression of GRWD1 is associated with increased cell proliferation, cell migration, epithelial–mesenchymal transition, and adverse outcomes in cancer[2][3][4]. No approved drugs currently target GRWD1 directly, but its central roles in chromatin architecture, DNA replication, and oncogenic signaling make it a potential target in oncology drug discovery.

Other names

GRWD1GRWDKIAA1942WDR28RRB1CDW4DIAR14CUL4- and DDB1-associated WDR protein 4WD repeat domain 28regulator of ribosome biogenesis 1 homolog

Drugs have not been specifically described, but hypothetical mechanisms include stabilization/disruption of GRWD1’s histone chaperone activity, interference with protein-protein interactions (such as GRWD1–RPL11–MDM2), or modulation of replication licensing.