タンパク質寿命が制御するシン・バイオロジー

Linear poly-ubiquitin chains, which are formed via the N-terminal methionine of ubiquitin, have been known as a unique non-degradable ubiquitin modification. Recently, we have found that linear ubiquitination contributes to proteasomal degradation and aggregate formation of aggregating proteins, mainly TDP-43, and that the abnormal accumulation of linear ubiquitin chains shifts the lifetime of a specific group of proteins. These suggest that linear ubiquitination may function as a novel post-translational modification that regulates protein lifetime. In this study, we will clarify the basic rules of the protein substrates whose lifetime is regulated by the presence or absence of linear poly-ubiquitin chain by comprehensive search and information analysis. Also, we will search for novel adaptor proteins and analyze known model substrates, to elucidate the molecular mechanism of linear poly-ubiquitin chain-dependent protein lifetime regulation.

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