Identification of a common subnuclear localization signal

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

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


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 3r](n, n≥1)+[L(φ/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+ (NoDSH+) 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.

Original languageEnglish (US)
Pages (from-to)3966-3977
Number of pages12
JournalMolecular biology of the cell
Issue number10
StatePublished - Oct 2007
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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