BIOL 141 |
| Secreted and transmembrane proteins mediate intercellular communication, driving pathophysiological processes such as inflammation, tumor angiogenesis, and metastasis. We recently discovered cotransin, a cyclodepsipeptide that inhibits the biogenesis of a subset of secretory proteins, including vascular endothelial growth factor (VEGF), an important cancer target. Cotransin blocks one of the earliest steps in the life of a secreted protein: translocation across the membrane of the endoplasmic reticulum (ER), a process that is directed by a signal sequence at the N-terminus of nascent secretory proteins. By an unknown mechanism, cotransin prevents the Sec61 translocation channel from gating in response to certain signal sequences, whereas the vast majority of signal sequences are unaffected. Here, I will describe recent synthetic and mechanistic studies that are beginning to reveal the molecular basis of cotransin's unprecedented biological activity. |
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Mechanism of Action of Natural Products
2:00 PM-4:40 PM, Tuesday, August 21, 2007 BCEC -- 109B, Oral
Division of Biological Chemistry |