Glutamate-rich WD repeat-containing protein 1 is a

WD40 repeat The WD40 repeat (also known as the WD or beta-transducin repeat) is a short structural motif of approximately 40 amino acids, often terminating in a tryptophan-aspartic acid (W-D) dipeptide. Tandem copies of these repeats typically fold togethe ...

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

(containing five WD40 repeat motifs) that in humans is encoded by the ''GRWD1''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. It localizes to the nucleus and has known functions in regulating

chromatin Chromatin is a complex of DNA and protein found in eukaryote, eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important r ...

accessibility and loading of the MCM helicase. GRWD1 has also been shown to play a critical role in

ribosome biogenesis Ribosome biogenesis is the process of making ribosomes. In prokaryotes, this process takes place in the cytoplasm with the transcription of many ribosome gene operons. In eukaryotes, it takes place both in the cytoplasm and in the nucleolus. ...

Role in cancer

While some ribosomal proteins like RPL5 and

RPL11 60S ribosomal protein L11 is a protein that in humans is encoded by the ''RPL11'' gene. Function Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are ...

are suggested to act as tumor suppressors by inhibiting E3 ubiquitin-protein ligase MDM2 and thus activating

p53 p53, also known as tumor protein p53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory transcription factor protein that is often mutated in human cancers. The p53 proteins (originally thou ...

, others, such as GRWD1, may promote

tumorigenesis Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cells are transformed into cancer cells. The process is characterized by changes at the cellular, genetic, and epigenetic levels and abn ...

. 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 Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events. Proteins responsible for detecting stimuli are generally termed receptors, although in some cases the term ...

, such as the

Notch signaling pathway The Notch signaling pathway is a highly Conserved sequence, conserved cell signaling system present in most animal, animals. Mammals possess four different Notch proteins, notch receptors, referred to as NOTCH1, NOTCH2, Notch 3, NOTCH3, and NOTC ...

, through the upregulation of

ADAM17 A disintegrin and metalloprotease 17 (ADAM17), also called TACE (''tumor necrosis factor-α-converting enzyme''), is a 70-kDa enzyme that belongs to the ADAM protein family of disintegrins and metalloproteases, activated by substrate presentatio ...

Role in cancer

References

Further reading