Regulation of follicle-stimulating hormone (FSH) synthesis is a central point of convergence for ... more Regulation of follicle-stimulating hormone (FSH) synthesis is a central point of convergence for signals controlling reproduction. The FSHbeta subunit is primarily regulated by gonadotropin-releasing hormone (GnRH), gonadal steroids, and activin. Here, we identify elements in the mouse FSHbeta promoter responsible for GnRH-mediated induction utilizing the LbetaT2 cell line that endogenously expresses FSH. The proximal 398 bp of the mouse FSHbeta promoter is sufficient for response to GnRH. This response localizes primarily to an AP-1 half-site (-72/-69) juxtaposed to a CCAAT box, which binds nuclear factor-Y. Both elements are required for AP-1 binding, creating a novel AP-1 site. Multimers of this site confer GnRH induction, and mutation or internal deletion of this site reduces GnRH induction by 35%. The same reduction was achieved using a dominant negative Fos protein. This is the only functional AP-1 site identified in the proximal 398 bp, since its mutation eliminates FSHbeta induction by c-Fos and c-Jun. GnRH regulation of the FSHbeta gene occurs through induction of multiple Fos and Jun isoforms, forming at least four different AP-1 molecules, all of which bind to this site. Mitogen-activated protein kinase activity is required for induction of FSHbeta and JunB protein. Finally, AP-1 interacts with nuclear factor-Y, which occupies its overlapping site in vivo.
Endonuclease G (Endo G) was identified as a DNase released from isolated murine liver mitochondri... more Endonuclease G (Endo G) was identified as a DNase released from isolated murine liver mitochondria treated with recombinant caspase-8 and full-length Bid (Li et al. 2001). Caspase-8 cleaves Bid into an active molecule capable of inducing mitochondrial outer membrane permeabilization (MOMP). Once MOMP occurs, several proteins are released from the intermembrane space to the cytoplasm, including Endo G. Bid-released Endo G can induce DNA degradation from isolated nuclei (Li et al. 2001).
Truncated Bid (tBid) and Bid BH3 peptides interact with Bak to induce cytochrome c release (Wei e... more Truncated Bid (tBid) and Bid BH3 peptides interact with Bak to induce cytochrome c release (Wei et al., 2000; Letai et al., 2002). The caspase-8 generated form of tBid (p15) may be the preferred activating form of tBid (Cartron et al., 2003). tBid induces a conformational change and oligomerization of Bak both in vitro and in vivo (Roucou et al., 2002). tBid does not cause release of cytochrome c release from purified Bak-deficient mitochondria.
The mitochondrial pathway of apoptosis in vertebrates is dependent on the process of mitochondria... more The mitochondrial pathway of apoptosis in vertebrates is dependent on the process of mitochondrial outer membrane permeabilization (MOMP), which leads to the release of proteins from the mitochondrial intermembrane space into the cytosol. "Upstairs" of this event are the Bcl-2 family proteins that regulate and mediate MOMP; "downstairs" is the activation of caspases that orchestrate the dismantling of the cell. In the Connections Map database at Science's Signal Transduction Knowledge Environment (STKE), the pathways that define the mitochondrial pathway of apotosis are illustrated, with the bulk of control occurring "upstairs" of MOMP.
Regulation of follicle-stimulating hormone (FSH) synthesis is a central point of convergence for ... more Regulation of follicle-stimulating hormone (FSH) synthesis is a central point of convergence for signals controlling reproduction. The FSHbeta subunit is primarily regulated by gonadotropin-releasing hormone (GnRH), gonadal steroids, and activin. Here, we identify elements in the mouse FSHbeta promoter responsible for GnRH-mediated induction utilizing the LbetaT2 cell line that endogenously expresses FSH. The proximal 398 bp of the mouse FSHbeta promoter is sufficient for response to GnRH. This response localizes primarily to an AP-1 half-site (-72/-69) juxtaposed to a CCAAT box, which binds nuclear factor-Y. Both elements are required for AP-1 binding, creating a novel AP-1 site. Multimers of this site confer GnRH induction, and mutation or internal deletion of this site reduces GnRH induction by 35%. The same reduction was achieved using a dominant negative Fos protein. This is the only functional AP-1 site identified in the proximal 398 bp, since its mutation eliminates FSHbeta induction by c-Fos and c-Jun. GnRH regulation of the FSHbeta gene occurs through induction of multiple Fos and Jun isoforms, forming at least four different AP-1 molecules, all of which bind to this site. Mitogen-activated protein kinase activity is required for induction of FSHbeta and JunB protein. Finally, AP-1 interacts with nuclear factor-Y, which occupies its overlapping site in vivo.
Endonuclease G (Endo G) was identified as a DNase released from isolated murine liver mitochondri... more Endonuclease G (Endo G) was identified as a DNase released from isolated murine liver mitochondria treated with recombinant caspase-8 and full-length Bid (Li et al. 2001). Caspase-8 cleaves Bid into an active molecule capable of inducing mitochondrial outer membrane permeabilization (MOMP). Once MOMP occurs, several proteins are released from the intermembrane space to the cytoplasm, including Endo G. Bid-released Endo G can induce DNA degradation from isolated nuclei (Li et al. 2001).
Truncated Bid (tBid) and Bid BH3 peptides interact with Bak to induce cytochrome c release (Wei e... more Truncated Bid (tBid) and Bid BH3 peptides interact with Bak to induce cytochrome c release (Wei et al., 2000; Letai et al., 2002). The caspase-8 generated form of tBid (p15) may be the preferred activating form of tBid (Cartron et al., 2003). tBid induces a conformational change and oligomerization of Bak both in vitro and in vivo (Roucou et al., 2002). tBid does not cause release of cytochrome c release from purified Bak-deficient mitochondria.
The mitochondrial pathway of apoptosis in vertebrates is dependent on the process of mitochondria... more The mitochondrial pathway of apoptosis in vertebrates is dependent on the process of mitochondrial outer membrane permeabilization (MOMP), which leads to the release of proteins from the mitochondrial intermembrane space into the cytosol. "Upstairs" of this event are the Bcl-2 family proteins that regulate and mediate MOMP; "downstairs" is the activation of caspases that orchestrate the dismantling of the cell. In the Connections Map database at Science's Signal Transduction Knowledge Environment (STKE), the pathways that define the mitochondrial pathway of apotosis are illustrated, with the bulk of control occurring "upstairs" of MOMP.
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Papers by Cheryl Bender