Fam65b Is a New Transcriptional Target of FOXO1 That Regulates RhoA Signaling for T Lymphocyte Migration | Zendy

Pablo Rougerie | Zendy; Quitterie Largeteau | Zendy; Laura Megrelis | Zendy; Florent Carrette | Zendy; Thomas Lejeune | Zendy; Lara Toffali | Zendy; Barbara Rossi | Zendy; Mahel Zeghouf | Zendy; Jacqueline Cherfils | Zendy; Gabriela Constantin | Zendy; Carlo Laudanna | Zendy; Georges Bismuth | Zendy; Marianne Mangeney | Zendy; Jérôme Delon | Zendy

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Fam65b Is a New Transcriptional Target of FOXO1 That Regulates RhoA Signaling for T Lymphocyte Migration

Author(s) -

Pablo Rougerie,

Quitterie Largeteau,

Laura Megrelis,

Florent Carrette,

Thomas Lejeune,

Lara Toffali,

Barbara Rossi,

Mahel Zeghouf,

Jacqueline Cherfils,

Gabriela Constantin,

Carlo Laudanna,

Georges Bismuth,

Marianne Mangeney,

Jérôme Delon

Publication year - 2012

Publication title -

the journal of immunology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.737

H-Index - 372

eISSN - 1550-6606

pISSN - 0022-1767

DOI - 10.4049/jimmunol.1201174

Subject(s) - rhoa , microbiology and biotechnology , foxo1 , small gtpase , gtpase , biology , chemokine receptor , cell adhesion , signal transduction , chemokine , cell , receptor , genetics , protein kinase b

Forkhead box O (FOXO) transcription factors favor both T cell quiescence and trafficking through their control of the expression of genes involved in cell cycle progression, adhesion, and homing. In this article, we report that the product of the fam65b gene is a new transcriptional target of FOXO1 that regulates RhoA activity. We show that family with sequence similarity 65 member b (Fam65b) binds the small GTPase RhoA via a noncanonical domain and represses its activity by decreasing its GTP loading. As a consequence, Fam65b negatively regulates chemokine-induced responses, such as adhesion, morphological polarization, and migration. These results show the existence of a new functional link between FOXO1 and RhoA pathways, through which the FOXO1 target Fam65b tonically dampens chemokine-induced migration by repressing RhoA activity.

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