Document Detail

Mtd/Bok takes a swing: proapoptotic Mtd/Bok regulates trophoblast cell proliferation during human placental development and in preeclampsia.
MedLine Citation:
PMID:  19942931     Owner:  NLM     Status:  MEDLINE    
We have previously reported that matador/Bcl-2 ovarian killer (Mtd/Bok), a proapoptotic member of the Bcl-2 family, regulates human trophoblast apoptosis and that its levels are elevated in severe preeclamptic pregnancy. Herein, we show that Mtd is also involved in the regulation of proliferation in normal and pathological placentae. Mtd was found in proliferating trophoblast cells during early placental development and in preeclampsia (PE). The main isoform of Mtd associated with trophoblast proliferation was Mtd-L, the full-length isoform, which preferentially localized to the nuclear compartment in proliferating cells, whereas during apoptosis it switched localization to the cytoplasm where it associated with mitochondria. Mtd expression in proliferating cells colocalized with cyclin E1, a G(1)/S phase cell cycle regulator. MtdL-specific knockdown in the early first trimester villous explants and in HEK293 revealed a direct effect of Mtd-L on cyclin E1 expression and cell cycle progression. We conclude that Mtd-L functions to regulate trophoblast cell proliferation during early placentation and that the elevated levels of Mtd found in PE may contribute to increased trophoblast proliferation accompanying this devastating disorder of pregnancy.
J E Ray; J Garcia; A Jurisicova; I Caniggia
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-11-27
Journal Detail:
Title:  Cell death and differentiation     Volume:  17     ISSN:  1476-5403     ISO Abbreviation:  Cell Death Differ.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-04-12     Completed Date:  2010-06-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9437445     Medline TA:  Cell Death Differ     Country:  England    
Other Details:
Languages:  eng     Pagination:  846-59     Citation Subset:  IM    
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Canada.
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MeSH Terms
Apoptosis / genetics,  physiology
Blotting, Western
Cell Line
Cell Line, Tumor
Cell Proliferation*
Cyclin E / metabolism
In Situ Nick-End Labeling
Oncogene Proteins / metabolism
Placentation / genetics,  physiology*
Pre-Eclampsia / metabolism*
Protein Isoforms / metabolism,  physiology
Proto-Oncogene Proteins c-bcl-2 / metabolism*,  physiology
Trophoblasts / cytology*,  metabolism*
Grant Support
MOP 62865//Canadian Institutes of Health Research
Reg. No./Substance:
0/BOK protein, human; 0/CCNE1 protein, human; 0/Cyclin E; 0/Oncogene Proteins; 0/Protein Isoforms; 0/Proto-Oncogene Proteins c-bcl-2

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