TP53 regulating kinase (TP53RK)

TP53 regulating kinase (TP53RK), also known as p53-related protein kinase (PRPK), is an atypical serine/threonine kinase that functions as a key regulatory subunit of the EKC/KEOPS complex. It plays an essential role in the modification of tRNAs (specifically the threonylcarbamoyl modification at position 37) and regulates protein phosphorylation events, including phosphorylation of p53 at serine 15, which enhances p53’s transcriptional and apoptotic activities[1][3][4][6]. TP53RK has additional p53-independent functions affecting cell survival, proliferation, telomere maintenance, and the proteasome pathway[7]. The protein localizes to the nucleus and cytoplasm. Mutations in TP53RK and its complex partners are associated with Galloway-Mowat syndrome, a rare congenital disorder, and increased vulnerability of TP53-deficient cancers to its inhibition makes it a potential cancer therapeutic target[1][2][4][5]. While no approved drugs directly target TP53RK, preclinical studies with PRPK inhibitors and combination with proteasome inhibition in cancer models have shown promise[3][7].

Other names

PRPKEKC/KEOPS complex subunit TP53RKC20orf64p53-related protein kinaseBUD32dJ101A2.2Nori-2pTPRKBatypical serine/threonine protein kinase TP53RKNori-2GAMOS4dJ101A2P53 regulating kinaseprpk

Small molecule inhibition of PRPK/TP53RK kinase activity; Dual targeting or synthetic lethality approaches in TP53-deficient cancers; Combination with proteasome inhibitors (e.g., bortezomib) to enhance cytotoxicity[7]