Novel Drug Targets for Multiple Diseases

Thursday, July 30, 2009 General News J E 4
Scientists at the University of Texas M.D. Anderson Cancer Center in Houston USA have identified several new drug targets to block G protein-coupled receptor (GPCR)-induced nuclear transcription factor kappa B (NF-kappaB) activation. GPCR is the biggest receptor family in human body. It elicits so important functions that Drs. Alfred G. Gilman and Martin Rodbell who discovered G-proteins were honored Nobel prize in 1994. Approximately 2% of the human genes encode GPCRs and they are widely expressed in almost all organs and play key roles in almost all physilogical functions. NF-kappaB was also first discovered in the lab of Nobel Prize laureate Dr. David Baltimore is. It binds DNA and critically regulates numerous gene expressions. Persistent activation of NF-kappaB contributes to many diseases such as cancer cardiovascular diseases neural diseases gastrointestinal diseases and immune diseases. Recently Dr. Sun and his colleagues have first identified that beta-arrestin 2 a signaling component under GPCR is indispensable to mediate GPCR-induced NF-kappaB activation. In beta-arrestin 2-deficient cells they found that NF-kappaB activation induced by GPCR activator like lysophosphatidic acid which is a diagnostic marker and pathogenesis factor in 90% ovarian cancer patients is completely blocked. This work has been published in Proceedings of the National Academy of Sciences of the United States of America. In their earlier work as the pioneers to study another novel adaptor protein CARMA3 they also revealed that CARMA3 is indispensable to mediate GPCR-induced NF-kappaB activation (Genes & Development) which was highly commented by "Science Signaling" as an important "Missing link to NF-kappaB". To further explore the mechanisms they first elucidated that beta-arrestin 2 recruits CARMA3 to GPCR thereby contributing to GPCR-induced NF-kappaB activation. Therefore two novel drug targets have been identified to block GPCR-induced NF-kappaB activation and related diseases. "It is an exciting breakthrough discovery. Although we still have a long way to go before we know about the clinical efficacy of this potential drug targets" said Dr. Sun "however because this novel signaling pathway ubiquitously exists in almost all cell types and diseases such as arthritis crohns disease cardiac ischemia-reperfusion injury and various types of cancers (brain lung liver lymphoma cervix) they will be ideal potential drug targets for multiple diseases and will benefit millions of people in the near future."


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