| First Author | Chen BB | Year | 2009 |
| Journal | Mol Cell Biol | Volume | 29 |
| Issue | 11 | Pages | 3062-75 |
| PubMed ID | 19332566 | Mgi Jnum | J:149141 |
| Mgi Id | MGI:3847817 | Doi | 10.1128/MCB.01824-08 |
| Citation | Chen BB, et al. (2009) Masking of a nuclear signal motif by monoubiquitination leads to mislocalization and degradation of the regulatory enzyme cytidylyltransferase. Mol Cell Biol 29(11):3062-75 |
| abstractText | Monoubiquitination aids in the nuclear export and entrance of proteins into the lysosomal degradative pathway, although the mechanisms are unknown. Cytidylyltransferase (CCTalpha) is a proteolytically sensitive lipogenic enzyme containing an NH(2)-terminal nuclear localization signal (NLS). We show here that CCTalpha is monoubiquitinated at a molecular site (K(57)) juxtaposed near its NLS, resulting in disruption of its interaction with importin-alpha, nuclear exclusion, and subsequent degradation within the lysosome. Cellular expression of a CCTalpha-ubiquitin fusion protein that mimics the monoubiquitinated enzyme resulted in cytoplasmic retention. A CCTalpha K(57R) mutant exhibited an extended half-life, was retained in the nucleus, and displayed proteolytic resistance. Importantly, by using CCTalpha-ubiquitin hybrid constructs that vary in the intermolecular distance between ubiquitin and the NLS, we show that CCTalpha monoubiquitination masks its NLS, resulting in cytoplasmic retention. These results unravel a unique molecular mechanism whereby monoubiquitination governs the trafficking and life span of a critical regulatory enzyme in vivo. |
