Antisense Depletion of Death-associated Protein Kinase Promotes Apoptosis

Yijun Jin, Patricia Gallagher

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Death-associated protein kinases (DAPK) are serine/ threonine protein kinases that have an important role in regulating cell death. In this study two antisense approaches were employed to down-regulate expression of the endogenous DAPK-α and DAPK-β proteins. Transient expression of an antisense DAPK cDNA or antisense morpholino oligonucleotides in HeLa, 3T3, or primary human vascular smooth muscle cells demonstrate that decreased DAPK expression promotes a spontaneous, caspase-mediated apoptosis as evidenced by increased activities of caspases-3 and -9. Clonal HeLa cell lines with attenuated levels of DAPK expression, obtained following selection in the presence of antisense DAPK cDNA, are more sensitive to tumor necrosis factor-induced caspase-mediated apoptosis, and their sensitivity is inversely related to DAPK expression. In contrast, HeLa cells with reduced DAPK expression are moderately resistant to cell death induced by interferon-γ. This finding is consistent with previous studies showing that DAPK has a role in promoting caspase-independent cell death. Together, these studies demonstrate that the cellular activities of DAPK are critical for antagonizing caspase-dependent apoptosis to promote cell survival under normal cell growth conditions.

Original languageEnglish
Pages (from-to)51587-51593
Number of pages7
JournalJournal of Biological Chemistry
Volume278
Issue number51
DOIs
StatePublished - Dec 19 2003

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Death-Associated Protein Kinases
Apoptosis
Caspases
Cell death
Cell Death
Protein-Serine-Threonine Kinases
Cells
HeLa Cells
Complementary DNA
Morpholinos
Caspase 9
Antisense Oligonucleotides
Cell growth
Vascular Smooth Muscle
Caspase 3
Interferons
Smooth Muscle Myocytes
Muscle

ASJC Scopus subject areas

  • Biochemistry

Cite this

Antisense Depletion of Death-associated Protein Kinase Promotes Apoptosis. / Jin, Yijun; Gallagher, Patricia.

In: Journal of Biological Chemistry, Vol. 278, No. 51, 19.12.2003, p. 51587-51593.

Research output: Contribution to journalArticle

Jin, Yijun ; Gallagher, Patricia. / Antisense Depletion of Death-associated Protein Kinase Promotes Apoptosis. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 51. pp. 51587-51593.
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