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Molecular and Cellular Biology, April 2004, p. 2797-2807, Vol. 24, No. 7
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.7.2797-2807.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Phosphorylation Controls Ikaros's Ability To Negatively Regulate the G1-S Transition

Pablo Gómez-del Arco, Kazushige Maki, and Katia Georgopoulos*

Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129

Received 14 November 2003/ Accepted 30 December 2003

Ikaros is a key regulator of lymphocyte proliferative responses. Inactivating mutations in Ikaros cause antigen-mediated lymphocyte hyperproliferation and the rapid development of leukemia and lymphoma. Here we show that Ikaros's ability to negatively regulate the G1-S transition can be modulated by phosphorylation of a serine/threonine-rich conserved region (p1) in exon 8. Ikaros phosphorylation in p1 is induced during the G1-S transition. Mutations that prevent phosphorylation in p1 increase Ikaros's ability to impede cell cycle progression and its affinity for DNA. Casein kinase II, whose increased activity in lymphocytes leads to transformation, is a key player in Ikaros p1 phosphorylation. We thus propose that Ikaros's activity as a regulator of the G1-S transition is controlled by phosphorylation in response to signaling events that downmodulate its DNA binding activity.

* Corresponding author. Mailing address: Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129. Phone: (617) 724-8279. Fax: (617) 726-4453. E-mail: katia.georgopoulos{at}cbrc2.mgh.harvard.edu.

Molecular and Cellular Biology, April 2004, p. 2797-2807, Vol. 24, No. 7
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.7.2797-2807.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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