QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 18, Issue 10, 3966-3977, October 2007

This Article Full Text Full Text (PDF) Supplemental Material All Versions of this Article: E07-03-0295v1 18/10/3966    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mekhail, K. Articles by Lee, S. Search for Related Content PubMed PubMed Citation Articles by Mekhail, K. Articles by Lee, S.

Identification of a Common Subnuclear Localization Signal

Karim Mekhail^*,, Luis Rivero-Lopez^*, Ahmad Al-Masri, Caroline Brandon, Mireille Khacho, and Stephen Lee

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

Submitted April 2, 2007; Revised June 26, 2007; Accepted July 13, 2007
Monitoring Editor: A. Gregory Matera

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)X₃r]_{(n, n1)}+[L(/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.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

* These authors contributed equally to this work.

These authors contributed equally to this work.

Present address: Department of Cell Biology, Harvard Medical School, Harvard University, 240 Longwood Avenue, Boston, MA 02115.

Address correspondence to: Stephen Lee (slee{at}uottawa.ca)

Abbreviations used: AP, acidification-permissive; B23, rRNA processing factor nucleophosmin; cIAP2, inhibitor of apoptosis 1; E3, ubiquitin ligase; FLIP, fluorescence loss in photobleaching; FRAP, fluorescence recovery after photobleaching; HIF, hypoxia-inducible factor; HSC70, heat-shock cognate 71-kDa protein; NES, nuclear export signal; NLS, nuclear localization signal; NoDS^H+, nucleolar detention signal regulated by [H⁺]; NoLS, nucleolar localization signal; NoRS, nucleolar retention signal; PBK1, ribosomal L1 domain–containing protein 1; RNF8, RING finger protein 8 ubiquitin ligase; SD medium, standard (medium); VHL, von Hippel-Lindau.

This article has been cited by other articles:

				M. Khacho, K. Mekhail, K. Pilon-Larose, A. Pause, J. Cote, and S. Lee eEF1A Is a Novel Component of the Mammalian Nuclear Protein Export Machinery Mol. Biol. Cell, December 1, 2008; 19(12): 5296 - 5308. [Abstract] [Full Text] [PDF]