The retinoblastoma protein (Rb) acts as a critical cell-cycle regulato
r and loss of Rb function is associated with a variety of human cancer
types. Here we report that Rb binds to members of the AP-1 family of
transcription factors, including c-Jun, and stimulates c-Jun transcrip
tional activity from an AP-1 consensus sequence. The interaction invol
ves the leucine zipper region of c-Jun and the B pocket of Rb as well
as a C-terminal domain. We also present evidence that the complexes ar
e found in terminally differentiating, keratinocytes and cells enterin
g the G(1) phase of the cell cycle after release from serum starvation
. The human papillomavirus type 16 E7 protein, which binds to both c-J
un and Rb, inhibits the ability of Rb to activate c-Jun. The results p
rovide evidence of a role for Rb as a transcriptional activates in ear
ly G(1) and as a potential modulator of c-Jun expression during kerati
nocyte differentiation.