The LIM-only protein FHL2 is a serum-inducible transcriptional coactivator of AP-1.
Proteins with LIM domains have been implicated in transcriptional regulation. The four and half LIM domain (FHL) group of LIM-only proteins is composed of five members, some of which have been shown to have intrinsic activation function. Here we show that FHL2 is the only member of the family whose expression is inducible upon serum stimulation in cultured cells. Induction of FHL2 is coordinated in time with the increased levels of two early-response products, the oncoproteins Fos and Jun. FHL2 associates with both Jun and Fos, in vitro and in vivo. The FHL2-Jun interaction requires the Ser-63-Ser-73 JNK phosphoacceptor sites in c-Jun, but not their phosphorylation. FHL2 powerfully stimulates Fos- and Jun-dependent transcription, thereby acting as an inducible coactivator of AP-1 function. Moreover, we show that intracellular localization of FHL2 is controlled by signaling events and a Crm1-dependent active nuclear export mechanism. Thus, FHL2, as an inducible coactivator of AP-1, coordinately participates with Fos and Jun in the early transcriptional response to serum factors.
Morlon
Aurore
A
Institut de Génétique et de Biologie Moléculaire et Cellulaire, B. P. 10142, 67404 Illkirch-Strasbourg, France.
Sassone-Corsi
Paolo
P
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects; D006801:Humans; D060588:LIM Domain Proteins; D060850:LIM-Homeodomain Proteins; D009124:Muscle Proteins; D015513:Oncogene Proteins / Q000235:genetics*; D016366:Open Reading Frames; D021381:Protein Transport / Q000528:radiation effects; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014157:Transcription Factors; D014162:Transfection; D014466:Ultraviolet Rays
D004268:DNA-Binding Proteins; C105987:FHL2 protein, human; D018398:Homeodomain Proteins; D060588:LIM Domain Proteins; D060850:LIM-Homeodomain Proteins; C065072:LMO1 protein, human; D009124:Muscle Proteins; D015513:Oncogene Proteins; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D005982:Glutathione Transferase