Identification of a common subnuclear localization signal.

Mol Biol Cell 2007 Oct 25;18(10):3966-77. Epub 2007 Jul 25.

Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ONT, Canada, K1H 8M5.

Proteins share peptidic sequences, such as a nuclear localization signal (NLS), which guide them to particular membrane-bound compartments. Similarities have also been observed within different classes of signals that target proteins to membrane-less subnuclear compartments. Common localization signals affect spatial and temporal subcellular organization and are thought to allow the coordinated response of different molecular networks to a given signaling cue. Here we identify a higher-order and predictive code, {[RR(I/L)X(3)r]((n, n > or = 1))+[L(phi/N)(V/L)]((n,n>1))}, that establishes high-affinity interactions between a group of proteins and the nucleolus in response to a specific signal. This position-independent code is referred to as a nucleolar detention signal regulated by H(+) (NoDS(H+)) and the class of proteins includes the cIAP2 apoptotic regulator, VHL ubiquitylation factor, HSC70 heat shock protein and RNF8 transcription regulator. By identifying a common subnuclear targeting consensus sequence, our work reveals rules governing the dynamics of subnuclear organization and ascribes new modes of regulation to several proteins with diverse steady-state distributions and dynamic properties.

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http://dx.doi.org/10.1091/mbc.e07-03-0295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1995723PMC
October 2007
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