FIF [fibroblast growth factor-2 (FGF-2)-interacting-factor], a nuclear putatively antiapoptotic factor, interacts specifically with FGF-2

Numerous evidence indicates that some of the activities of fibroblast growt h factor 2 (FGF-2) depend on an intracrine mode of action. Recently, we sho wed that three high molecular mass (HMM) nuclear forms of FGF-2 are part of a 320-kDa protein complex while the cytoplasmic AUG-initiated form is incl uded in a 130-kDa complex. Consequently, the characterization of FGF endoge nous targets has become crucial to allow the elucidation of their endogenou s activities. Through the screening of GAL4-based yeast two-hybrid expressi on libraries, we have isolated a gene encoding a nuclear protein of 55 kDa, FIF (FGF2-interacting-factor), which interacts specifically with FGF2 but not with FGF-1, FGF-3, or FGF-6. In this system, FIF interacts equally well with the NH2-extended 24-kDa FGF form as with the 18-kDa form, indicating that the FIF-binding motif is located in the last 155 amino acids of FGF-2. Nevertheless, coimmunoprecipitation experiments showed an exclusive associ ation with HMM FGF-2. The predicted protein contains a canonical leucine zi pper domain and three overlapping hydrophobic heptad repeats. The region sp anning these repeats is, together with a region located in the N-terminal p art of the FIF protein, implicated in the binding to FGF-2. In contrast to the full-length FIF protein, several deletion constructs were able to trans activate a lac-Z reporter gene. Furthermore, the COOH-terminal part, but no t the full-length FIF protein, has previously been shown to exhibit antiapo ptotic properties. Thus we discuss the possibility that these activities co uld reflect a physiological function of FIF through its interaction with FG F-2.