Biology:DAPK1
 Generic protein structure example |
Death-associated protein kinase 1 is an enzyme that in humans is encoded by the DAPK1 gene.[1]
Function
Death-associated protein kinase 1 is a positive mediator of gamma-interferon induced programmed cell death. DAPK1 encodes a structurally unique 160-kD calmodulin dependent serine-threonine kinase that carries 8 ankyrin repeats and 2 putative P-loop consensus sites. It is a tumor suppressor candidate.[2]
In melanocytic cells DAPK1 gene expression may be regulated by MITF.[3]
As a drug target
Depletion of DAPK1 results in inhibition of tumor cell count and volume growth in cellular and animal models of triple receptor-negative breast cancer, from individuals with p53-mutant cancers.[4] This has not been demonstrated in actual patients.
References
- ↑ "Assignment of DAP1 and DAPK--genes that positively mediate programmed cell death triggered by IFN-gamma--to chromosome regions 5p12.2 and 9q34.1, respectively". Genomics 29 (1): 305–7. Sep 1995. doi:10.1006/geno.1995.1255. PMID 8530096.
- ↑ "Entrez Gene: DAPK1 death-associated protein kinase 1". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1612.
- ↑ "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell & Melanoma Research 21 (6): 665–76. Dec 2008. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971.
- ↑ "Death-associated protein kinase 1 promotes growth of p53-mutant cancers". The Journal of Clinical Investigation 125 (7): 2707–20. Jul 2015. doi:10.1172/JCI70805. PMID 26075823.
Further reading
- "Identification of a novel serine/threonine kinase and a novel 15-kD protein as potential mediators of the gamma interferon-induced cell death". Genes & Development 9 (1): 15–30. Jan 1995. doi:10.1101/gad.9.1.15. PMID 7828849.
- "Death-associated protein kinase-related protein 1, a novel serine/threonine kinase involved in apoptosis". Molecular and Cellular Biology 20 (3): 1044–54. Feb 2000. doi:10.1128/MCB.20.3.1044-1054.2000. PMID 10629061.
- "Identification of a new form of death-associated protein kinase that promotes cell survival". The Journal of Biological Chemistry 276 (43): 39667–78. Oct 2001. doi:10.1074/jbc.M101886200. PMID 11485996.
- "The pro-apoptotic function of death-associated protein kinase is controlled by a unique inhibitory autophosphorylation-based mechanism". The Journal of Biological Chemistry 276 (50): 47460–7. Dec 2001. doi:10.1074/jbc.M105133200. PMID 11579085.
- "Aberrant promoter methylation of multiple genes in bronchial brush samples from former cigarette smokers". Cancer Research 62 (2): 351–5. Jan 2002. PMID 11809677.
- "Overexpression of translocation-associated fusion genes of FGFRI, MYC, NPMI, and DEK, but absence of the translocations in acute myeloid leukemia. A microarray analysis". Haematologica 87 (6): 569–77. Jun 2002. PMID 12031912.
- "Patterns of gene promoter methylation in squamous cell cancer of the head and neck". Oncogene 21 (27): 4231–6. Jun 2002. doi:10.1038/sj.onc.1205528. PMID 12082610.
- "A death-associated protein kinase (DAPK)-interacting protein, DIP-1, is an E3 ubiquitin ligase that promotes tumor necrosis factor-induced apoptosis and regulates the cellular levels of DAPK". The Journal of Biological Chemistry 277 (49): 46980–6. Dec 2002. doi:10.1074/jbc.M208585200. PMID 12351649.
- "DAP-kinase induces apoptosis by suppressing integrin activity and disrupting matrix survival signals". The Journal of Cell Biology 159 (1): 169–79. Oct 2002. doi:10.1083/jcb.200204050. PMID 12370243.
- "Hypermethylation of death-associated protein (DAP) kinase CpG island is frequent not only in B-cell but also in T- and natural killer (NK)/T-cell malignancies". Cancer Science 94 (1): 87–91. Jan 2003. doi:10.1111/j.1349-7006.2003.tb01357.x. PMID 12708480.
- "Ca2+-dependent phosphorylation of syntaxin-1A by the death-associated protein (DAP) kinase regulates its interaction with Munc18". The Journal of Biological Chemistry 278 (28): 26265–74. Jul 2003. doi:10.1074/jbc.M300492200. PMID 12730201.
- "Frequent death-associated protein-kinase promoter hypermethylation in brain metastases of solid tumors". Oncology Reports 10 (4): 1031–3. 2004. doi:10.3892/or.10.4.1031. PMID 12792765.
- "Prognostic significance of death-associated protein-kinase expression in hepatocellular carcinomas". Anticancer Research 23 (2B): 1333–41. 2003. PMID 12820391.
- "Expression of death-associated protein kinase and recruitment to the tumor necrosis factor signaling pathway following brief seizures". Journal of Neurochemistry 86 (5): 1260–70. Sep 2003. doi:10.1046/j.1471-4159.2003.01934.x. PMID 12911633.
- "Aberrant methylation of DAP-kinase in therapy-related acute myeloid leukemia and myelodysplastic syndromes". Blood 103 (2): 698–700. Jan 2004. doi:10.1182/blood-2003-07-2249. PMID 14504087.
- "Antisense depletion of death-associated protein kinase promotes apoptosis". The Journal of Biological Chemistry 278 (51): 51587–93. Dec 2003. doi:10.1074/jbc.M309165200. PMID 14530257.
- "Promoter methylation and down-regulation of DAPK is associated with gastric atrophy". International Journal of Molecular Medicine 12 (6): 827–30. Dec 2003. doi:10.3892/ijmm.12.6.827. PMID 14612952.
- "Reduced expression of death-associated protein kinase in human uterine and ovarian carcinoma cells". Oncology Reports 11 (3): 661–5. Mar 2004. doi:10.3892/or.11.3.661. PMID 14767518.
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