Bioinformatics and Systems Medicine Laboratory
General information | Expression | Regulation | Mutation | Interaction

Basic Information

Gene ID

1613

Name

DAPK3

Synonymous

ZIP|ZIPK;death-associated protein kinase 3;DAPK3;death-associated protein kinase 3

Definition

DAP kinase 3|DAP-like kinase|MYPT1 kinase|ZIP kinase isoform|ZIP-kinase|dlk|zipper-interacting protein kinase

Position

19p13.3

Gene type

protein-coding

Source

Count: 1; Generif

Sentence

Abstract

"Results suggest that DAPK3 is a tumor suppressor in which loss-of-function mutations promote increased cell survival, proliferation, cellular aggregation."

cancer kinome sequencing studies have identified several protein kinases predicted to possess driver (i.e., causal) mutations. Using bioinformatic applications, we have pinpointed DAPK3 (ZIPK) as a novel cancer-associated kinase with functional mutations. Evaluation of nonsynonymous point mutations, discovered in DAPK3 in various tumors (T112M, D161N, and P216S), reveals that all three mutations decrease or abolish kinase activity. Furthermore, phenotypic assays indicate that the three mutations observed in cancer abrogate the function of the kinase to regulate both the cell cycle and cell survival. Coexpression of wild-type (WT) and cancer mutant kinases shows that the cancer mutants dominantly inhibit the function of the WT kinase. Reconstitution of a non-small cell lung cancer cell line that harbors an endogenous mutation in DAPK3 (P216S) with WT DAPK3 resulted in decreased cellular aggregation and increased sensitivity to chemotherapy. Our results suggest that DAPK3 is a tumor suppressor in which loss-of-function mutations promote increased cell survival, proliferation, cellular aggregation, and increased resistance to chemotherapy.CI - (c)2011 AACR.

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