AP-1 complex is effector of Hox-induced cellular proliferation and transformation

Hox gene products, initially characterized as master regulators of embryoni c patterning, are also required for proper functioning of adult tissues. Th ere is also a growing body of evidence that links Hox proteins to regulatio n of cellular proliferation/transformation. However, the underlying molecul ar mechanisms of Hox-associated transformation and tissue growth have yet t o be elucidated. Using a well established model system for studying changes in cellular proliferation induced by Hoxb4, we show that AP-I activity is markedly increased in Hoxb4-transduced cells due to significant upregulatio n of Jun-B and Fra-1 protein levels, Furthermore, we also show that the spe cific changes in AP-1 protein expression are necessary for the proliferatio n effects induced by Hoxb4, and that these changes converge to increase lev els of cyclin D1, a known integrator of proliferation signals. Our observat ions thus link Hox gene products with key elements of the cell cycle machin ery.