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Embryo implantation is essential for normal pregnancy, and the process of decidualization is critical for embryo implantation. However, the mechanism of decidualization during early pregnancy is still unknown. Forkhead box O3a (FOXO3a) is the most important functional transcription factor of the forkhead box family and is a highly conserved transcription factor of apoptosis‐related genes. In the mouse uterus, FOXO3a was found to be expressed regularly from Days 1–7 of early pregnancy. Upon further exploration, it was found that FOXO3a was expressed at significantly higher levels at the implantation site than at the interimplantation site on Days 5–7 of pregnancy. Under artificial decidualization, FOXO3a was highly expressed in the first and second decidual zones. After decidualization, the expression of FOXO3a was significantly increased both in vivo and vitro. In primary stromal cells, apoptosis was reduced by decreased expression of FOXO3a after inducing decidualization. Moreover, when FOXO3a‐small interfering RNA was transfected into the uteri of mice, the expression of decidualization‐ and apoptosis‐related factors was impaired. Thus, FOXO3a might play an important role in decidualization during early pregnancy, and cell apoptosis might be one of pathways for FOXO3a‐regulated decidualization. Embryo implantation is essential for normal pregnancy, and the process of decidualization is critical for embryo implantation. The expression of forkhead box O3a (FOXO3a) was significantly increased when decidualization both in vivo and vitro. FOXO3a might play an important role in decidualization during early pregnancy. [ABSTRACT FROM AUTHOR]

The 14-3-3 proteins associate with many cellular proteins that participate in the regulation of various cellular events including apoptosis, the cell cycle, spreading, and migration. We have previously described that 14-3-3 binds the 1-integrin and overexpression of 14-3-3 promoted increased cell spreading and migration (Han et al. [2001] Oncogene 20: 346357). In this study, we find that mutation of Ser 60 of 14-3-3, outside of the amphipathic groove which is involved in 14-3-3 protein interactions with other ligands, abolished its interaction with integrin. Surprisingly, this mutant retained its ability to promote cell spreading, suggesting that 14-3-3 interaction with the 1-integrin is not required for its regulation of cell adhesion. We next showed that mutations of several critical residues in the amphipathic groove did not affect 14-3-3 interaction with the 1-integrin. As expected, these mutants disrupted their association with the phosphoserine dependent ligands Raf and Cas. Analysis of the groove mutant LF (mutation of Arg129Tyr130 to Leu and Phe) indicated that, unlike wild type 14-3-3, it could not stimulate cell spreading or migration, suggesting that a functional amphipathic groove is required for 14-3-3 regulation of cell adhesion and migration. Consistent with this, cells expressing the LF mutant exhibited a delay in F-actin organization compared to cells expressing wild type or the S60A mutant (Ser 60 to Ala mutation) upon cell adhesion to fibronectin (FN). Taken together, these studies identified a novel binding site on 14-3-3 for integrin 1 and showed that a functional amphipathic groove, rather than its interaction with integrin 1, is required for 14-3-3 regulation of cell spreading and migration. 2005 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Cover: The cover image, by Long et al., is based on the Original Research Article, FOXO3a is essential for murine endometrial decidualization through cell apoptosis during early pregnancy, DOI: 10.1002/jcp.27167. [ABSTRACT FROM AUTHOR]