Search results

Search:
in the keywords: KINASE

Sort By:

Limit search:

Transcriptional regulation in thymic epithelial cells for the establishment of self tolerance

100%

Matsumoto M.

Archivum Immunologiae et Therapiae Experimentalis

2007

vol. 55

issue 1

27-34

Thymic epithelial cells (TECs) play pivotal roles in the establishment of self tolerance through critical dialogue with developing thymocytes. Unique actions of two transcriptional regulators within TECs, NF-kB-inducing kinase (NIK) and an autoimmune regulator (AIRE), for the establishment of self tolerance have recently been highlighted by studies using a strain of mouse bearing a natural mutation of the NIK gene (aly mice) and gene-targeted mice, respectively. Previous studies have demonstrated essential roles of NIK downstream of the lymphotoxin-beta receptor (LTbetaR), which is essential for the development of secondary lymphoid organs; aly mice lack all lymph nodes and Peyer's patches because of the defective LTbetaR signaling. Additional roles of NIK in thymic organogenesis downstream of LTbetaR, mainly through the developmental regulation of TECs, have now emerged, although the corresponding ligand(s) for LTbetaR participating in this action have not been fully characterized. In contrast, AIRE, a gene responsible for the development of an organ-specific autoimmune disease that demonstrates monogenic autosomal recessive inheritance, contributes to the establishment of self tolerance probably by controlling the expression of self antigens through yet undetermined molecular mechanisms. Thus it is highly likely that a group of genes control self-tolerance within TECs through unique and coordinated actions, and that an understanding of this process would help to unravel the pathogenesis of autoimmune disease.

Anti-tumor chemotherapy utilizing peptide-based approaches ? apoptotic pathways, kinases, and proteasome as targets

100%

Mendoza F. J., Espino P. S., Cann K. L., Bristow N., Mc_Crea K., Los M.

Archivum Immunologiae et Therapiae Experimentalis

2005

vol. 53

issue 1

47-60

The pharmacological sciences are taking advantage of recent discoveries that have defined the molecular pathways governing apoptosis. These signaling cascades are frequently inactivated or distorted by mutations in cancer cells. Peptides derived from critical interaction, phosphorylation, or cleavage sites are the preferred leads (starting points) for the development of new drugs. In this review we summarize recent peptide-based approaches that target MDM2, p53, NF-?B, ErbB2, MAPK, as well as Smac/DIABLO, IAP BIR domains, and Bcl-2 interaction domains, with a specific focus on the BH3 domain. Separate parts of the review deal with proteasome inhibitors, integrin-derived peptides, and molecules that are being tested for tumor-selective delivery of anticancer drugs ('magic bullet' approach). The proteasome inhibitors and integrin-derived peptides show a variety of effects, targeting not only tumor growth, but also angiogenesis, metastasizing potential, and other cancer cell functions. The last part of this review describes approaches that use specific properties (surface receptors, increased enzymatic activities) of cancer cells in order to target them specifically. These new generations of anticancer drugs provide the foundations for therapies with fewer side effects and higher efficacy.

Refine search results

2 Archivum Immunologiae et Therapiae Experimentalis

1 2007

1 2005

1 Bristow N.

1 Cann K. L.

1 Espino P. S.

1 Los M.

1 Matsumoto M.

1 Mc_Crea K.

1 Mendoza F. J.

Search results

Transcriptional regulation in thymic epithelial cells for the establishment of self tolerance

Anti-tumor chemotherapy utilizing peptide-based approaches ? apoptotic pathways, kinases, and proteasome as targets