title: Fam65b is a new transcriptional target of FOXO1 that regulates RhoA signaling for T lymphocyte migration.
abstract: 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.
authors.affiliation: INSERM, U1016, Institut Cochin, 75014 Paris, France.
authors.forename: Pablo
authors.initials: P
authors.lastname: Rougerie
authors.forename: Quitterie
authors.initials: Q
authors.lastname: Largeteau
authors.forename: Laura
authors.initials: L
authors.lastname: Megrelis
authors.forename: Florent
authors.initials: F
authors.lastname: Carrette
authors.forename: Thomas
authors.initials: T
authors.lastname: Lejeune
authors.forename: Lara
authors.initials: L
authors.lastname: Toffali
authors.forename: Barbara
authors.initials: B
authors.lastname: Rossi
authors.forename: Mahel
authors.initials: M
authors.lastname: Zeghouf
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Cherfils
authors.forename: Gabriela
authors.initials: G
authors.lastname: Constantin
authors.forename: Carlo
authors.initials: C
authors.lastname: Laudanna
authors.forename: Georges
authors.initials: G
authors.lastname: Bismuth
authors.forename: Marianne
authors.initials: M
authors.lastname: Mangeney
authors.forename: Jérôme
authors.initials: J
authors.lastname: Delon
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D015815:Cell Adhesion Molecules; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics*; D018925:Chemokines / Q000494:pharmacology; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D011485:Protein Binding; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D015533:Transcriptional Activation; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; D018925:Chemokines; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D011506:Proteins; C104952:RIPOR2 protein, human; D020742:rhoA GTP-Binding Protein