Researchers at University of Iowa publish new data on enzyme research
2009 JUL 13 - (NewsRx.com) -- "Monoubiquitination aids in the nuclear export and entrance of proteins into the lysosomal degradative pathway, although the mechanisms are unknown. Cytidylyltransferase (CCT alpha) is a proteolytically sensitive lipogenic enzyme containing an NH2-terminal nuclear localization signal (NLS)," scientists in the United States report. "We show here that CCT alpha 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 CCT alpha-ubiquitin fusion protein that mimics the monoubiquitinated enzyme resulted in cytoplasmic retention. A CCT alpha K-57R mutant exhibited an extended half-life, was retained in the nucleus, and displayed proteolytic resistance. Importantly, by using CCT alpha-ubiquitin hybrid constructs that vary in the intermolecular distance between ubiquitin and the NLS, we show that CCT alpha monoubiquitination masks its NLS, resulting in cytoplasmic retention," wrote B.B. Chen and colleagues, University of Iowa. The researchers concluded: "These results unravel a unique molecular mechanism whereby monoubiquitination governs the trafficking and life span of a critical regulatory enzyme in vivo.." Chen and colleagues published their study in Molecular and Cellular Biology (Masking of a Nuclear Signal Motif by Monoubiquitination Leads to Mislocalization and Degradation of the Regulatory Enzyme Cytidylyltransferase. Molecular and Cellular Biology, 2009;29(11):3062-3075). For more information, contact R.K. Mallampalli, University of Iowa, Dept. of Internal Medical, Division Pulmology & Critical Care, Roy J & Lucille A Carver College Medical, C-33K, GH, Iowa City, IA 52242, USA. Publisher contact information for the journal Molecular and Cellular Biology is: American Society Microbiology, 1752 N St. NW, Washington, DC 20036-2904, USA. Keywords: United States, Iowa City, Cellular, Cytidylyltransferase, Enzyme Research, Proteomics. Fusion Proteins, University of Iowa. This article was prepared by Proteomics Weekly editors from staff and other reports. Copyright 2009, Proteomics Weekly via NewsRx.com.
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