Selective inhibitor of c-Fos and their antiproliferative properties The invention relates to selective inhibitor of c-Fos for use in the prevention and/or treatment of cancers and restenosis.

A method of treating a mammalian subject with cancer comprises administering to said subject having a cancer, e.g., a metastatic or refractory cancer or tumor, a small molecule inhibitor of a target signaling molecule of the MEK/MAPK pathway that impairs T cell activation, and administering to said subject a molecule that induces T cell proliferation in the presence of said inhibitor. The combination of a small molecule inhibitor of a target of the MEK/MAPK pathway and the T cell proliferation inducer reduces the proliferation of the cancer and tumor cells in vivo. Compositions and kits including these components are also provided.

Disclosed are compositions and methods for treating a disease and/or disorder such as cancer in a subject in need thereof. In some embodiments, the method includes administering to the subject a nucleic acid construct that includes a first nucleic acid sequence having a promoter operably linked to each of a second nucleic acid sequence encoding a therapeutic polypeptide, and a third nucleic acid sequence encoding a peptide domain that is stabilized when phosphorylated by stress-activated kinase activity in a target cell and/or tissue. In some embodiments, the target cell and/or tissue is a cell and/or tissue undergoing a stress response. In some embodiments, the kinase activity is stress-activated kinase activity mediated by p38/MAP14 kinase activity, INK activity, or both.

The present disclosure provides modulators of proteasome dynamics and/or function in a mammalian cell, compositions and uses thereof. The disclosed modulating compounds are characterized by affecting at least one of: mammalian target of rapamycin (mTOR) activation and/or lysosomal association, proteasome cellular localization, the activity and/or level/s and/or the post translational modification/s (PTM/s), and/or subcellular localization of at least one signaling molecule participating directly or indirectly in at least one pathway mediating said proteasome dynamics/function.

A method of identifying a subject having cancer who is likely to benefit from treatment with a combination therapy with a RAF inhibitor and a second inhibitor is provided. A method of treating cancer in a subject in need thereof is also provided and includes administering to the subject an effective amount of a RAF inhibitor and an effective amount of a second inhibitor, wherein the second inhibitor is a MEK inhibitor, a CRAF inhibitor, a CrkL inhibitor or a TPL2/COT inhibitor. A method of identifying a kinase target that confers resistance to a first inhibitor is also provided.

The present invention provides compositions and methods for treating epidermolysis bullosa.

In alternative embodiments, provided are compositions and methods for manipulating the exchange of water and/or carbon dioxide (CO.sub.2) through plant stomata comprising the step of modulating the expression of CO.sub.2 sensor genes and the redundant MAP kinases MPK4/MPK12, and HT1 protein kinase, and their genes. In alternative embodiments, provided are dominant active HT1 mutants that cause a high CO2-insensitive constitutively open stomatal phenotype. In alternative embodiments, the invention provides plants, and plant tissues, having increased water use efficiency, and drought-resistant plants, plant tissues and cells; and methods for engineering of water transpiration and water use efficiency in plants, and engineering plants with increased water use efficiency and drought-resistant plants, plant tissues and cells. For plants grown in humid regions with sufficient water availability, down-regulation of the CO2 sensor proteins provides plants that show less stomatal closing in light of the atmospheric CO2 increase for enabling enhanced CO2 influx into leaves.