Abstract p62 is a cytoplasmic ubiquitin chain binding protein. Upon a variety of extracellular signals, both transcript and protein levels of p62 were rapidly increased. These signals include phorbol 12-myristate 13-acetate (PMA) and calcium ionomycin for peripheral blood mononuclear cells, serum or PDGF for serum-starved NIH3T3 cells, IL-3 for the G1 arrested pre-B cell line Ba/F3, and PMA for a human promyelocyte line U937. The elevation of p62 transcript level is due to temporal stabilization of mRNA and rapid activation of the p62 gene. Cycloheximide-induced enhanced transcription suggests the immediate early response of the p62 gene. The rapid induction of p62 indicates the presence of a novel ubiquitination-mediated regulatory mechanism during cell proliferation and differentiation.