Calcineurin-dependent nuclear import of the transcription factor Crz1p requires Nmd5p

Citation
Rs. Polizotto et Ms. Cyert, Calcineurin-dependent nuclear import of the transcription factor Crz1p requires Nmd5p, J CELL BIOL, 154(5), 2001, pp. 951-960
Citations number
46
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
JOURNAL OF CELL BIOLOGY
ISSN journal
0021-9525 → ACNP
Volume
154
Issue
5
Year of publication
2001
Pages
951 - 960
Database
ISI
SICI code
0021-9525(20010903)154:5<951:CNIOTT>2.0.ZU;2-X
Abstract
Calcineurin is a conserved Ca2+/calmodulin-specific serine-threonine protei n phosphatase that mediates many Ca2+-dependent signaling events. In yeast, calcineurin dephosphorylates Crz1p, a transcription factor that binds to t he calcineurin-dependent response element, a 24-bp promoter element. Calcin eurin-dependent dephosphorylation of Crz1p alters Crz1p nuclear localizatio n. This study examines the mechanism by which calcineurin regulates the nuc lear localization of Crz1p in more detail. We describe the identification a nd characterization of a novel nuclear localization sequence (NLS) in Crz1p , which requires both basic and hydrophobic residues for activity, and show that the karyopherin Nmd5p is required for Crz1p nuclear import. We also d emonstrate that the binding of Crz1p to Nmd5p is dependent upon its phospho rylation state, indicating that nuclear import of Crz1p is regulated by cal cineurin. Finally, we demonstrate that residues in both the NH2- and COOH-t erminal portions of Crz1p are required for regulated Crz1p binding to Nmd5p , supporting a model of NLS masking for regulating Crz1p nuclear import.