Glucocorticoid action and novel mechanisms of steroid resistance: role of glucocorticoid receptor-interacting proteins for glucocorticoid responsiveness.
Glucocorticoids are widely used to treat inflammatory and malignant diseases. However, many individuals show a lack of therapeutic response and unwanted side-effects. Various known and unknown parameters determine glucocorticoid responsiveness, among them glucocorticoid receptor (GR)-interacting proteins. Several of the proteins interacting with GR also participate in other signal transduction pathways such as the AP-1 pathway and the nuclear factor-kappaB pathway. We suggest that a closer study of GR-interacting proteins may shed new light on mechanisms determining glucocorticoid sensitivity. In this commentary, the general mechanisms of GR action will be addressed and a proteomic-based method to study GR-interacting proteins will be described in brief.
Wikström
A-C
AC
Department of Medical Nutrition, Karolinska Institutet, Novum, S-141 86 Huddinge, Sweden. lotta.wikstrom@mednut.ki.se
D048948:14-3-3 Proteins; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000627:therapeutic use*; D003600:Cytosol / Q000378:metabolism; D004351:Drug Resistance; D015180:Electrophoresis, Gel, Two-Dimensional; D004591:Electrophoresis, Polyacrylamide Gel; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D007525:Isoelectric Focusing; D008099:Liver / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D048948:14-3-3 Proteins; D000893:Anti-Inflammatory Agents; D016328:NF-kappa B; D011965:Receptors, Glucocorticoid; D014446:Tyrosine 3-Monooxygenase; D019908:Proto-Oncogene Proteins c-raf