Homeodomain-interacting protein kinase 2 (HIPK2) (HIPK2)

Homeodomain-interacting protein kinase 2 (HIPK2) is a member of the dual-specificity tyrosine-regulated kinase (DYRK) family that functions as a coregulator for a diverse set of transcription factors [UniProt: P52657]. It plays a pivotal role in the DNA damage response by phosphorylating p53 at Serine 46, a modification that specifically triggers the expression of pro-apoptotic genes [PubMed: 11242104]. In addition to its role in apoptosis, HIPK2 regulates several signaling pathways, including TGF-beta, Wnt/beta-catenin, and Notch, which are essential for development and tissue homeostasis [PubMed: 22534343]. Dysregulation of HIPK2 is linked to various pathologies; it often acts as a tumor suppressor in cancer, but its overexpression is associated with the progression of renal and hepatic fibrosis [PubMed: 25341105]. Although no FDA-approved drugs currently target HIPK2, small molecule inhibitors are being explored in preclinical models to mitigate fibrosis and modulate chemoresistance in oncology [PubMed: 31431614].

Other names

HIPK2hHIPK2PRO0593

HIPK2 acts as a serine/threonine kinase that phosphorylates downstream targets such as p53, CtBP, and Smad proteins to regulate gene transcription and cellular responses to stress [PubMed: 22534343].