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. GRWD1 has also been shown to play a critical role in ribosome biogenesis.

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. In addition to its interaction with RPL11, GRWD1 directly interacts with wild-type p53, suppressing its transcriptional activity. 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.