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Gene Review

HIPK3  -  homeodomain interacting protein kinase 3

Homo sapiens

Synonyms: ANPK, Androgen receptor-interacting nuclear protein kinase, DYRK6, FIST, FIST3, ...
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Disease relevance of HIPK3

  • In conclusion, we present novel evidence that JNK regulates the expression of HIPK3 in prostate cancer cells, and this contributes to increased resistance to Fas receptor-mediated apoptosis by reducing the interaction between FADD and caspase-8 [1].
  • The catalytic kinase domain of ANPK shares considerable sequence similarity with the minibrain gene product, a protein kinase suggested to contribute to learning defects associated with Down syndrome [2].

High impact information on HIPK3

  • Although Fas ligand-induced activation of Jun NH(2)-terminal kinase is impaired by overexpressed active FIST/HIPK3, cell death is not affected [3].
  • JNK regulates HIPK3 expression and promotes resistance to Fas-mediated apoptosis in DU 145 prostate carcinoma cells [1].
  • HIPK3 has also been reported to phosphorylate FADD [1].
  • The proteins contain a conserved protein kinase domain that is separated from a domain that interacts with homeoproteins and hence are termed homeodomain-interacting protein kinases (HIPKs): HIPK1, HIPK2, and HIPK3 [4].
  • In this work, we have characterized a novel 130-kDa Ser/Thr protein kinase ANPK that interacts with the zinc finger region of AR in vivo and in vitro [2].

Biological context of HIPK3


Associations of HIPK3 with chemical compounds


Other interactions of HIPK3

  • The interaction between FADD and caspase-8 was inhibited, but abrogation of JNK activity or HIPK3 expression was found to restore this interaction and increased the sensitivity of DU 145 cells to Fas receptor-mediated apoptosis [1].


  1. JNK regulates HIPK3 expression and promotes resistance to Fas-mediated apoptosis in DU 145 prostate carcinoma cells. Curtin, J.F., Cotter, T.G. J. Biol. Chem. (2004) [Pubmed]
  2. Activation of androgen receptor function by a novel nuclear protein kinase. Moilanen, A.M., Karvonen, U., Poukka, H., Jänne, O.A., Palvimo, J.J. Mol. Biol. Cell (1998) [Pubmed]
  3. FIST/HIPK3: a Fas/FADD-interacting serine/threonine kinase that induces FADD phosphorylation and inhibits fas-mediated Jun NH(2)-terminal kinase activation. Rochat-Steiner, V., Becker, K., Micheau, O., Schneider, P., Burns, K., Tschopp, J. J. Exp. Med. (2000) [Pubmed]
  4. Homeodomain-interacting protein kinases, a novel family of co-repressors for homeodomain transcription factors. Kim, Y.H., Choi, C.Y., Lee, S.J., Conti, M.A., Kim, Y. J. Biol. Chem. (1998) [Pubmed]
  5. Assignment of the protein kinase homolog of YAK1 (HIPK3) to human chromosome band 11p13 by in situ hybridization. Nupponen, N.N., Visakorpi, T. Cytogenet. Cell Genet. (1999) [Pubmed]
  6. Androgen-receptor-interacting nuclear proteins. Jänne, O.A., Moilanen, A.M., Poukka, H., Rouleau, N., Karvonen, U., Kotaja, N., Häkli, M., Palvimo, J.J. Biochem. Soc. Trans. (2000) [Pubmed]
  7. Identification and sequence of human PKY, a putative kinase with increased expression in multidrug-resistant cells, with homology to yeast protein kinase Yak1. Begley, D.A., Berkenpas, M.B., Sampson, K.E., Abraham, I. Gene (1997) [Pubmed]
  8. Discontinuing the phenylalamine-restricted diet in young children with PKY. Psychosocial aspects. Pueschel, S.M., Yeatman, S., Hum, C. Journal of the American Dietetic Association. (1977) [Pubmed]
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