Protein levels in the cell represent the sum of synthesis and degradation. The protein's (genetically encoded) amino acid sequence specifies not only the protein's structure, but also its lifetime through hidden degradation signals encoded in the sequence. Degradation rates balance gene expression rates and thus represent the second half of the equation that determines the active concentration of proteins. In the same way that aberrant gene expression is linked to cancer, so too is aberrant protein processing or degradation. The identity of a protein given by its amino is also dynamic and a combination of sequence elements encoding a degradation initiation signal and a degradation stop signal control the formation of protein fragments with activities distinct from those of the full length protein. This project will decode the sequence signals that shape the proteome and will determine the mechanical and chemical principles underlying these mechanisms.
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