The p56(lck)-interacting protein p62 stimulates transcription via the SV40enhancer

p62 is a recently identified ubiquitin-binding, cytosolic phosphoprotein th at interacts with several signal transduction molecules including the tyros ine kinase p56(lck) and the protein kinase C-zeta, p62 is therefore suggest ed to serve an important role in signal transduction in the cell, although the physiological function of p62 remains undefined. Here we demonstrate by transient transfection assays that p62 stimulates the transcription of rep orter genes linked to the simian virus 40 (SV40) enhancer. A putative p62-r esponsive element was localized to the B domain of the distal 72-base pair repeat of the SV40 enhancer. p62 was unable to bind this element in vitro, nor was it able to activate transcription when directly tethered to a promo ter, suggesting that p62 stimulates transcription via an indirect mechanism . Stimulation of transcription mediated by p62 was dependent on its amino-t erminal region, which is also necessary for interaction with cell surface s ignaling molecules. These findings indicate that p62 may link extracellular signals directly to transcriptional responses, and identify the SV40 enhan cer as a downstream target for signal transduction pathways in which p62 pa rticipates.