Cleanin' house: protein quality control in the nucleus.
Richard G. Gardner, Zara W. Nelson, Daniel E. Gottschling
Division of Basic Sciences, Fred Hutchinson CRC, 1100 Fairview Ave N., Seattle, WA, 98109, USA
Correct sequence and proper structure are critical for the function of DNA, RNA, and protein. To minimize the negative effects of synthesis errors or damage-induced abnormalities, the cell engages a variety of quality control (QC) processes that function in proofreading, repair, and removal. One cellular compartment where QC may especially important is the nucleus. Here, a battery of QC processes function to maintain the integrity of the DNA code and to ensure the fidelity of information transfer during transcription. Although nuclear quality control is well established for DNA and RNA, nothing is known about how protein quality is managed in the nucleus, despite the fact that virtually every nuclear process relies on protein action. Accordingly, we have initiated studies in yeast to discover components of nuclear protein QC. By identifying a common suppressor of several temperature-sensitive mutant nuclear proteins, we uncovered a RING-domain ubiquitin-protein ligase, San1p, which acts to target mutant nuclear proteins for ubiquitination and subsequent destruction by the proteasome. As expected for a dedicated nuclear protein QC pathway, San1p is localized to the nucleus and its localization is required for function. Of six temperature-sensitive nuclear proteins tested thus far, San1p is involved in the degradation of four, indicating that San1p-dependent ubiquitination may be the dominant pathway for nuclear protein QC degradation.
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