17 research outputs found
Intrinsically active MEK variants are differentially regulated by proteinases and phosphatases
MAPK/ERK kinase (MEK) 1/2 are central signaling proteins that serve as specificity determinants of the MAPK/ERK cascade. More than twenty activating mutations have been reported for MEK1/2, and many of them are known to cause diseases such as cancers, arteriovenous malformation and RASopathies. Changes in their intrinsic activity do not seem to correlate with the severity of the diseases. Here we studied four MEK1/2 mutations using biochemical and molecular dynamic methods. Although the studied mutants elevated the activating phosphorylation of MEK they had no effect on the stimulated ERK1/2 phosphorylation. Studying the regulatory mechanism that may explain this lack of effect, we found that one type of mutation affects MEK stability and two types of mutations demonstrate a reduced sensitivity to PP2A. Together, our results indicate that some MEK mutations exert their function not only by their elevated intrinsic activity, but also by modulation of regulatory elements such as protein stability or dephosphorylation
Proteomic database mining opens up avenues utilizing extracellular protein phosphorylation for novel therapeutic applications
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LOWER THAN PREDICTED HEART RATE RESPONSE TO MAX VO2 TESTING IN HIV-1 DISEASE1174
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Effect of acute exercise on lymphocyte enumeration in HIV+ African-American women
Tanshinone I inhibited growth of human chronic myeloid leukemia cells via JNK/ERK mediated apoptotic pathways
Pigment epithelium-derived factor as an anticancer drug and new treatment methods following the discovery of its receptors: A patent perspective
Traditional forms of cancer therapy, which include chemotherapy, have largely been overhauled due to the significant degree of toxicity they pose to normal, otherwise healthy tissue. It is hoped that the use of biological agents, most of which are endogenously present in the body, will lead to safer treatment outcomes, without sacrificing efficacy. The finding that pigment epithelium-derived factor (PEDF), a naturally-occurring protein, is a potent angiogenesis inhibitor has become the basis for studying the role of PEDF in tumours that are highly resistant to chemotherapy. The determination of the direct role of PEDF against cancer paves the way for understanding and developing PEDF as a novel drug. This review focuses on the patent applications behind testing the anticancer therapeutic effect of PEDF via its receptors as an antiangiogenic agent and as a direct anticancer agent. The majority of the PEDF patents describe the antiangiogenic ability and usage of recombinant vectors as the mode of treatment delivery. PEDF's therapeutic potential against different diseases and the discovery of its receptors open possibilities for improving PEDF-based peptide design and drug delivery modes