Histone Demethylases KDM4A and KDM4C Regulate Differentiation of Embryonic Stem Cells to Endothelial Cells.

Understanding epigenetic mechanisms regulating embryonic stem cell (ESC) differentiation to endothelial cells may lead to increased efficiency of generation of vessel wall endothelial cells needed for vascular engineering. Here we demonstrated that the histone demethylases KDM4A and KDM4C played an indispensable but independent role in mediating the expression of fetal liver kinase (Flk)1 and VE-cadherin, respectively, and thereby the transition of mouse ESCs (mESCs) to endothelial cells. KDM4A was shown to bind to histones associated with the Flk1 promoter and KDM4C to bind to histones associated with the VE-cadherin promoter.

Active demethylation of the IL-2 Promoter in CD4+ T cells is mediated by an inducible DNA glycosylase, Myh.

Epigenetic control of tissue-specific gene expression is often achieved by active demethylation of promoter regions; however, the nature of all the enzymes mediating this remodeling process is not fully clear. Here we describe a 5-methylcytosine glycosylase activity for the murine DNA base excision repair enzyme Myh and show that it is critically involved in remodeling the IL-2 Promoter for transcription. The enzyme is not expressed in naïve CD4(+) T cells, but can be transiently induced following T cell activation.

CD45 recruits adapter protein DOK-1 and negatively regulates JAK-STAT signaling in hematopoietic cells.

It has been extensively documented that CD45 positively regulates T cell receptor-mediated signaling through the activation of Src-family kinases. The mechanism whereby CD45 negatively regulates the JAK/STAT pathway, however, has not been fully elucidated. Here we describe the mechanism by which CD45 negatively regulates the JAK/STAT pathway through the recruitment of the inhibitory molecule Downstream of Kinase 1 (DOK-1) in hematopoietic cells.

Structure and functional characterization of single-strand DNA binding protein SSDP1: carboxyl-terminal of SSDP1 has transcription activity.

LIM-homeodomain transcription factors control a wide range of developmental processes, such as early patterning of the embryonic development, organ formations of brain, limbs, and eyes. Molecular mechanisms of the underlying processes involve complicated multiple protein complexes that direct transcription activation of target genes, protein-protein interactions, and transcriptional regulations. Among those molecules, cofactor Ldb1, interacting with LIM/homeobox family transcription factor, defines a tetrameric protein complex in controlling downstream genes of transcriptional regulation.

PTEN associates with the vault particles in HeLa cells.

PTEN is a tumor suppressor that primarily dephosphorylates phosphatidylinositol 3,4,5-trisphosphate to down-regulate the phosphoinositide 3-kinase/Akt signaling pathway. Although the cellular functions of PTEN as a tumor suppressor have been well characterized, the mechanism by which PTEN activity is modulated by other signal molecules in vivo remains poorly understood. In searching for potential PTEN modulators through protein-protein interaction, we identified the major vault protein (MVP) as a dominant PTEN-binding protein in a yeast two-hybrid screen.

SKAP55 recruits to lipid rafts and positively mediates the MAPK pathway upon T cell receptor activation.

T cell receptor (TCR) engagement triggers a series of events including protein tyrosine kinase activation, tyrosine phosphorylation of adapter proteins, and multiple protein-protein interactions. We observed that adapter protein SKAP55, the Src kinase-associated phosphoprotein, formed homodimers through its SH3 domain and SK region. SKAP55 as a substrate interacted with Fyn kinase in vivo.

SKAP55 coupled with CD45 positively regulates T-cell receptor-mediated gene transcription.

CD45 plays a critical role in T-cell receptor (TCR)-mediated signaling. In a yeast two-hybrid screen, SKAP55, the Src kinase-associated phosphoprotein of unknown function, was found as a substrate which associated with CD45 in vivo. Mutational analysis demonstrated the pivotal role of Tyr-232 in SKAP55 in the association with CD45.