p53-related protein kinase (TP53RK) (TP53RK)

p53-related protein kinase (TP53RK), also known as PRPK or BUD32, is a serine/threonine kinase that plays a critical role in regulating the p53 tumor suppressor and serves as a core component of the KEOPS (Kinase, Endopeptidase, and Other Proteins of Small size) complex (UniProt Q96S44; Abe et al., 2001). It is primarily responsible for phosphorylating p53 at the Ser15 residue, an action that stabilizes p53 and enhances its transcriptional activity in response to DNA damage (Abe et al., 2001). Beyond its interaction with p53, TP53RK is essential for the universal N6-threonylcarbamoyladenosine (t6A) modification of tRNA, which is vital for accurate translation initiation and protein synthesis (Braun et al., 2017). In oncology, TP53RK is frequently overexpressed in various malignancies, including multiple myeloma and colorectal cancer, where it promotes cell proliferation and survival, making it an attractive therapeutic target (Hideshima et al., 2015). Small molecule inhibitors targeting the kinase activity of TP53RK, such as HI-TOPK-032, are currently being explored to induce apoptosis in cancer cells, although challenges remain regarding the potential impact on essential tRNA modification processes in healthy tissues (Hideshima et al., 2015; Braun et al., 2017).

Other names

PRPKBUD32Nori-2TP53RKp53-related protein kinaseBUD32 homolog

Inhibition of the kinase activity of TP53RK, which prevents the phosphorylation of p53 at the Ser15 residue and disrupts the KEOPS complex-mediated N6-threonylcarbamoyladenosine (t6A) modification of tRNA (Hideshima et al., 2015; UniProt Q96S44).