Runx-dependent expression of PKC is critical for cell survival in the sea urchin embryo.

Runx-dependent expression of PKC is critical for cell survival in the sea urchin embryo.
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DOI:
10.1186/1741-7007-3-18
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发表时间:
2005-08-02
期刊:
影响因子:
5.4
通讯作者:
Coffman JA
Coffman JA
中科院分区:
生物学2区
文献类型:
--
作者:
Dickey-Sims C;Robertson AJ;Rupp DE;McCarthy JJ;Coffman JA

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Runx transcription factors play critical roles in the developmental control of cell fate and contribute variously as oncoproteins and tumor suppressors to leukemia and other cancers. To discover fundamental Runx functions in the cell biology of animal development, we have employed morpholino antisense-mediated knockdown of the sea urchin Runx protein SpRunt-1. Previously we showed that embryos depleted of SpRunt-1 arrest development at early gastrula stage and underexpress the conventional protein kinase C SpPKC1. We report here that SpRunt-1 deficiency leads to ectopic cell proliferation and extensive apoptosis. Suppression of the apoptosis by pharmacological inhibition of caspase-3 prevents the ectopic proliferation and rescues gastrulation, indicating that many of the overt defects obtained by knockdown of SpRunt-1 are secondary to the apoptosis. Inhibition or knockdown of SpPKC1 also causes apoptosis, while cell survival is rescued in SpRunt-1 morphant embryos coinjected with SpPKC1 mRNA, suggesting that the apoptosis associated with SpRunt-1 deficiency is caused by the deficit in SpPKC1 expression. Chromatin immunoprecipitation indicates that SpRunt-1 interacts physically with SpPKC1 in vivo, and cis-regulatory analysis shows that this interaction activates SpPKC1 transcription. Our results show that Runx-dependent activation of SpPKC1 is essential for maintaining protein kinase C activity at levels conducive to cell survival during embryogenesis.
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发表时间: 2002-04-15
影响因子: 4.1
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影响因子: 4.8
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发表时间: 2004-05-24
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