We describe c-Jun, a widely studied transcription factor that participates in cell proliferation, differentiation, and tumorigenesis, as amphitropic. We show that c-Jun forms stable monolayers and interacts favorably, although in a nonselective manner, with phospholipids at the interface. The surface activity of c-Jun, together with that of c-Fos, its common partner in AP-1 transcription heterodimers, drives interfacial complex formation. We show that AP-1 is very stable at the air-water interface and suggest that AP-1 may not be substantially formed in solution as a stable equimolar association of both proteins. (c) 2005 Elsevier Inc. All rights reserved.