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Gene Review

DAPK1  -  death-associated protein kinase 1

Homo sapiens

Synonyms: DAP kinase 1, DAPK, Death-associated protein kinase 1
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Disease relevance of DAPK1


Psychiatry related information on DAPK1


High impact information on DAPK1

  • The DAPk family has been linked to several cell death-related signaling pathways, and functions other than cell death have also been proposed [8].
  • Death-associated protein kinase (DAPk) is the founding member of a newly classified family of Ser/Thr kinases, whose members not only possess significant homology in their catalytic domains, but also share cell death-associated functions [8].
  • The realization that DAPk is a tumor suppressor gene, whose expression is lost in multiple tumor types, has spurred a flurry of interest in the kinase family and produced an impressive body of literature concerning its function, regulation, and connection to disease [8].
  • The second is transcribed into a single 6.3-kb mRNA and codes for a unique 160-kD calmodulin-dependent serine/threonine kinase (DAP kinase) that carries eight ankyrin repeats [9].
  • DAP-kinase is a positive mediator of apoptosis induced by certain cytokines and oncogenes [10].

Chemical compound and disease context of DAPK1


Biological context of DAPK1


Anatomical context of DAPK1


Associations of DAPK1 with chemical compounds


Physical interactions of DAPK1

  • These data suggest that DAPK-1 forms a multiprotein survival complex with cathepsin B countering the rate of TNFR-1-dependent apoptosis and highlights the importance of developing DAPK-1 inhibitors as agents to sensitize cells to stress-induced apoptosis [23].

Enzymatic interactions of DAPK1

  • Furthermore, DAP kinase phosphorylates ZIP kinase at six specific sites within its extracatalytic C-terminal domain [24].

Regulatory relationships of DAPK1


Other interactions of DAPK1


Analytical, diagnostic and therapeutic context of DAPK1


  1. Promoter hypermethylation patterns of p16, O6-methylguanine-DNA-methyltransferase, and death-associated protein kinase in tumors and saliva of head and neck cancer patients. Rosas, S.L., Koch, W., da Costa Carvalho, M.G., Wu, L., Califano, J., Westra, W., Jen, J., Sidransky, D. Cancer Res. (2001) [Pubmed]
  2. Frequent aberrant promoter hypermethylation of O6-methylguanine-DNA methyltransferase and death-associated protein kinase genes in immunodeficiency-related lymphomas. Rossi, D., Gaidano, G., Gloghini, A., Deambrogi, C., Franceschetti, S., Berra, E., Cerri, M., Vendramin, C., Conconi, A., Viglio, A., Muti, G., Oreste, P., Morra, E., Paulli, M., Capello, D., Carbone, A. Br. J. Haematol. (2003) [Pubmed]
  3. Chronic HIV type 1 infection down-regulates expression of DAP kinase and p19ARF-p53 checkpoint and is associated with resistance to CD95-mediated apoptosis in HUT78 T cells. Kim, C.H., Chiplunkar, S., Gupta, S. AIDS Res. Hum. Retroviruses (2004) [Pubmed]
  4. Frequent death-associated protein-kinase promoter hypermethylation in brain metastases of solid tumors. Gonzalez-Gomez, P., Bello, M.J., Alonso, M.E., Lomas, J., Arjona, D., Amiñoso, C., De Campos, J.M., Isla, A., Gutierrez, M., Rey, J.A. Oncol. Rep. (2003) [Pubmed]
  5. Patterns of gene promoter methylation in squamous cell cancer of the head and neck. Hasegawa, M., Nelson, H.H., Peters, E., Ringstrom, E., Posner, M., Kelsey, K.T. Oncogene (2002) [Pubmed]
  6. DAPK1 variants are associated with Alzheimer's disease and allele-specific expression. Li, Y., Grupe, A., Rowland, C., Nowotny, P., Kauwe, J.S., Smemo, S., Hinrichs, A., Tacey, K., Toombs, T.A., Kwok, S., Catanese, J., White, T.J., Maxwell, T.J., Hollingworth, P., Abraham, R., Rubinsztein, D.C., Brayne, C., Wavrant-De Vrièze, F., Hardy, J., O'Donovan, M., Lovestone, S., Morris, J.C., Thal, L.J., Owen, M., Williams, J., Goate, A. Hum. Mol. Genet. (2006) [Pubmed]
  7. Aberrant promoter methylation in bronchial epithelium and sputum from current and former smokers. Belinsky, S.A., Palmisano, W.A., Gilliland, F.D., Crooks, L.A., Divine, K.K., Winters, S.A., Grimes, M.J., Harms, H.J., Tellez, C.S., Smith, T.M., Moots, P.P., Lechner, J.F., Stidley, C.A., Crowell, R.E. Cancer Res. (2002) [Pubmed]
  8. The death-associated protein kinases: structure, function, and beyond. Bialik, S., Kimchi, A. Annu. Rev. Biochem. (2006) [Pubmed]
  9. Identification of a novel serine/threonine kinase and a novel 15-kD protein as potential mediators of the gamma interferon-induced cell death. Deiss, L.P., Feinstein, E., Berissi, H., Cohen, O., Kimchi, A. Genes Dev. (1995) [Pubmed]
  10. TGF-beta induces apoptosis through Smad-mediated expression of DAP-kinase. Jang, C.W., Chen, C.H., Chen, C.C., Chen, J.Y., Su, Y.H., Chen, R.H. Nat. Cell Biol. (2002) [Pubmed]
  11. Multiplicity of abnormal promoter methylation in lung adenocarcinomas from smokers and never smokers. Divine, K.K., Pulling, L.C., Marron-Terada, P.G., Liechty, K.C., Kang, T., Schwartz, A.G., Bocklage, T.J., Coons, T.A., Gilliland, F.D., Belinsky, S.A. Int. J. Cancer (2005) [Pubmed]
  12. Aberrant CpG island hypermethylation profile is associated with atypical and anaplastic meningiomas. Liu, Y., Pang, J.C., Dong, S., Mao, B., Poon, W.S., Ng, H.K. Hum. Pathol. (2005) [Pubmed]
  13. Aberrant promoter hypermethylation of the death-associated protein kinase gene is early and frequent in murine lung tumors induced by cigarette smoke and tobacco carcinogens. Pulling, L.C., Vuillemenot, B.R., Hutt, J.A., Devereux, T.R., Belinsky, S.A. Cancer Res. (2004) [Pubmed]
  14. DNA methylation in anal intraepithelial lesions and anal squamous cell carcinoma. Zhang, J., Martins, C.R., Fansler, Z.B., Roemer, K.L., Kincaid, E.A., Gustafson, K.S., Heitjan, D.F., Clark, D.P. Clin. Cancer Res. (2005) [Pubmed]
  15. Bidirectional signals transduced by DAPK-ERK interaction promote the apoptotic effect of DAPK. Chen, C.H., Wang, W.J., Kuo, J.C., Tsai, H.C., Lin, J.R., Chang, Z.F., Chen, R.H. EMBO J. (2005) [Pubmed]
  16. Death-associated protein kinase-related protein 1, a novel serine/threonine kinase involved in apoptosis. Inbal, B., Shani, G., Cohen, O., Kissil, J.L., Kimchi, A. Mol. Cell. Biol. (2000) [Pubmed]
  17. Gene promoter hypermethylation in tumors and serum of head and neck cancer patients. Sanchez-Cespedes, M., Esteller, M., Wu, L., Nawroz-Danish, H., Yoo, G.H., Koch, W.M., Jen, J., Herman, J.G., Sidransky, D. Cancer Res. (2000) [Pubmed]
  18. Death-associated protein kinase expression in human temporal lobe epilepsy. Henshall, D.C., Schindler, C.K., So, N.K., Lan, J.Q., Meller, R., Simon, R.P. Ann. Neurol. (2004) [Pubmed]
  19. Evaluation of hypermethylated tumor suppressor genes as tumor markers in mouth and throat rinsing fluid, nasopharyngeal swab and peripheral blood of nasopharygeal carcinoma patient. Chang, H.W., Chan, A., Kwong, D.L., Wei, W.I., Sham, J.S., Yuen, A.P. Int. J. Cancer (2003) [Pubmed]
  20. The tumor suppressor DAP kinase is a target of RSK-mediated survival signaling. Anjum, R., Roux, P.P., Ballif, B.A., Gygi, S.P., Blenis, J. Curr. Biol. (2005) [Pubmed]
  21. Hypermethylation of the death-associated protein kinase promoter attenuates the sensitivity to TRAIL-induced apoptosis in human non-small cell lung cancer cells. Tang, X., Wu, W., Sun, S.Y., Wistuba, I.I., Hong, W.K., Mao, L. Mol. Cancer Res. (2004) [Pubmed]
  22. DAP-kinase induces apoptosis by suppressing integrin activity and disrupting matrix survival signals. Wang, W.J., Kuo, J.C., Yao, C.C., Chen, R.H. J. Cell Biol. (2002) [Pubmed]
  23. Identification of a dominant negative functional domain on DAPK-1 that degrades DAPK-1 protein and stimulates TNFR-1-mediated apoptosis. Lin, Y., Stevens, C., Hupp, T. J. Biol. Chem. (2007) [Pubmed]
  24. Death-associated protein kinase phosphorylates ZIP kinase, forming a unique kinase hierarchy to activate its cell death functions. Shani, G., Marash, L., Gozuacik, D., Bialik, S., Teitelbaum, L., Shohat, G., Kimchi, A. Mol. Cell. Biol. (2004) [Pubmed]
  25. Death associated protein kinase: from regulation of apoptosis to tumor suppressive functions and B cell malignancies. Ng, M.H. Apoptosis (2002) [Pubmed]
  26. Structure of the UNC5H2 death domain. Handa, N., Kukimoto-Niino, M., Akasaka, R., Murayama, K., Terada, T., Inoue, M., Yabuki, T., Aoki, M., Seki, E., Matsuda, T., Nunokawa, E., Tanaka, A., Hayashizaki, Y., Kigawa, T., Shirouzu, M., Yokoyama, S. Acta Crystallogr. D Biol. Crystallogr. (2006) [Pubmed]
  27. Histone deacetylase 5 is not a p53 target gene, but its overexpression inhibits tumor cell growth and induces apoptosis. Huang, Y., Tan, M., Gosink, M., Wang, K.K., Sun, Y. Cancer Res. (2002) [Pubmed]
  28. Promoter hypermethylation of p16INK4a, E-cadherin, O6-MGMT, DAPK and FHIT in adenocarcinomas of the esophagus, esophagogastric junction and proximal stomach. Schildhaus, H.U., Kröckel, I., Lippert, H., Malfertheiner, P., Roessner, A., Schneider-Stock, R. Int. J. Oncol. (2005) [Pubmed]
  29. Promoter methylation status of multiple genes in brain metastases of solid tumors. Gonzalez-Gomez, P., Bello, M.J., Alonso, M.E., Amiñoso, C., Lopez-Marin, I., De Campos, J.M., Isla, A., Gutierrez, M., Rey, J.A. Int. J. Mol. Med. (2004) [Pubmed]
  30. Differential DNA methylation profiles in gynecological cancers and correlation with clinico-pathological data. Yang, H.J., Liu, V.W., Wang, Y., Tsang, P.C., Ngan, H.Y. BMC Cancer (2006) [Pubmed]
  31. Prognostic implication of aberrant promoter hypermethylation of CpG islands in adenocarcinoma of the lung. Kim, Y.T., Park, S.J., Lee, S.H., Kang, H.J., Hahn, S., Kang, C.H., Sung, S.W., Kim, J.H. J. Thorac. Cardiovasc. Surg. (2005) [Pubmed]
  32. Frequent death-associated protein kinase promoter hypermethylation in multiple myeloma. Ng, M.H., To, K.W., Lo, K.W., Chan, S., Tsang, K.S., Cheng, S.H., Ng, H.K. Clin. Cancer Res. (2001) [Pubmed]
  33. Methylation of tumour suppressor genes APAF-1 and DAPK-1 and in vitro effects of demethylating agents in bladder and kidney cancer. Christoph, F., Kempkensteffen, C., Weikert, S., K??llermann, J., Krause, H., Miller, K., Schostak, M., Schrader, M. Br. J. Cancer (2006) [Pubmed]
  34. Promoter methylation of DAP-kinase: association with advanced stage in non-small cell lung cancer. Kim, D.H., Nelson, H.H., Wiencke, J.K., Christiani, D.C., Wain, J.C., Mark, E.J., Kelsey, K.T. Oncogene (2001) [Pubmed]
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