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Molecular and Cellular Biology, February 2002, p. 1126-1139, Vol. 22, No. 4
0270-7306/01/$04.00+0     DOI: 10.1128/MCB.22.4.1126-1139.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Unique Motif for Nucleolar Retention and Nuclear Export Regulated by Phosphorylation

Frédéric Catez,1,{dagger} Monique Erard,2 Nathalie Schaerer-Uthurralt,1 Karine Kindbeiter,1 Jean-Jacques Madjar,1,{ddagger} and Jean-Jacques Diaz1*

INSERM U369, Faculté de Médecine Lyon-René Théophile Hyacinthe Laennec, 69372 Lyon Cedex 08,1 Institut de Pharmacologie et de Biologie Structurale, 31077 Toulouse Cedex 4, France2

Received 26 July 2001/ Returned for modification 7 September 2001/ Accepted 8 November 2001

By microinjecting purified glutathione S-transferase linked to all or parts of herpes simplex virus type 1 US11 protein into either the nucleus or the cytoplasm, we have demonstrated that this nucleolar protein exhibits a new type of localization signal controlling both retention in nucleoli and export to the cytoplasm. Saturated mutagenesis combined with computer modeling allowed us to draw the fine-structure map of this domain, revealing a new proline-rich motif harboring both activities, which are temperature dependent and regulated by phosphorylation. Finally, crossing the nuclear pore complex from the cytoplasm to the nucleus is an energy-dependent process for US11 protein, while getting to nucleoli through the nucleoplasm is energy independent.

* Corresponding author. Mailing address: INSERM U369, Faculté de Médecine Lyon-R.T.H. Laennec, 7, Rue Guillaume Paradin, 69372 Lyon Cedex 08, France. Phone: 33-(0)4-78-77-87-17. Fax: 33-(0)4-78-77-87-36. E-mail: diaz{at}laennec.univ-lyon1.fr.

{dagger} Present address: Protein Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.

{ddagger} Present address: DIAMB, Université Claude Bernard Lyon-1, 69622 Villeurbanne Cedex, France.

Molecular and Cellular Biology, February 2002, p. 1126-1139, Vol. 22, No. 4
0022-538X/01/$04.00+0     DOI: 10.1128/MCB.22.4.1126-1139.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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