Analysis: Degradation signals correlate with protein half-life

I yesterday blogged about how the protein half-life data from the O’Shea lab fit well with my earlier analyses of transcriptional regulation during the budding yeast cell cycle and with the just-in-time assembly hypothesis. However, I have now realized that the same data set can be used to test the validity of the sequence-based predictions of protein degradation signals that I relied on for the cell-cycle study.

To this end, I divided the budding yeast proteome into six groups: proteins with a D-box, proteins without a D-box, proteins with a KEN-box, proteins without a KEN-box, proteins with a PEST region, and proteins without a PEST region. For each of these six groups of proteins, I simply plotted the distribution of protein half-lives as a histogram:

The figure shows that for all three degradation signals, proteins with the sequence motif tend to have shorter half-lives than proteins without the motif. These differences are all statistically significant according to the Mann-Whitney U test (D-box, P < 10-6; KEN-box, P < 0.02; PEST region, P < 10-15). It is noteworthy that the KEN-box motif gives a far weaker correlation with protein half-live than the two other degradation signals, as it was also the only degradation signal that did not correlate with transcriptional cell-cycle regulation in budding yeast (see supplementary information of Jensen et al., 2006).

In summary, proteins that contain putative degradation signals have significantly shorter half-lives than proteins that do not contain such signals. The only caveat is that long sequences are more likely to match the sequence motifs, and that O’Shea and colleagues found a negative correlation between sequence length and protein half-life. The correlations described here could thus be a secondary effect; however, it is also possible that the presence of degradation signals in long sequences is the missing explanation for their short half-lives.

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