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SUMMARY:Deciphering the role of post-translational modifications in p53 re
 gulation with protein semisynthesis - Dr. Manuel Muller 
DTSTART:20210421T093000Z
DTEND:20210421T103000Z
UID:TALK159394@talks.cam.ac.uk
CONTACT:Anne Jacobs
DESCRIPTION:The tumour suppressor protein p53 orchestrates the response to
  cell damage and thus plays a central role in preventing cancer. p53 is ti
 ghtly regulated by post-translational modifications (PTMs). The precise me
 chanisms through which p53 PTMs operate are difficult to elucidate due to 
 the complexity of p53 signalling and challenges associated with preparing 
 site-specifically modified p53 for in vitro studies. To address these issu
 es\, we have developed a protein semi-synthesis strategy to access p53 in 
 defined PTM states. Using such ‘designer’ phospho-p53 variants we have
  probed the mechanism of p53 activation through phosphorylation in vitro. 
 Moreover\, we found that a spontaneous protein backbone modification\, the
  rearrangement of an asparagine to an isoaspartate residue\, reconfigures 
 p53’s binding partner specificity\, which suggests that p53 could act as
  a molecular time bomb. Given the importance of PTMs in p53 signalling\, w
 e believe that our chemistry-driven approach will contribute greatly to a 
 mechanistic understanding of how this protein makes cellular life and deat
 h decisions. 
LOCATION:https://zoom.us/j/95477079823
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