The p56(lck)-interacting protein p62 stimulates transcription via the SV40 enhancer.
p62 is a recently identified ubiquitin-binding, cytosolic phosphoprotein that interacts with several signal transduction molecules including the tyrosine kinase p56(lck) and the protein kinase C-zeta. p62 is therefore suggested 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 reporter genes linked to the simian virus 40 (SV40) enhancer. A putative p62-responsive 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 promoter, suggesting that p62 stimulates transcription via an indirect mechanism. Stimulation of transcription mediated by p62 was dependent on its amino-terminal region, which is also necessary for interaction with cell surface signaling molecules. These findings indicate that p62 may link extracellular signals directly to transcriptional responses, and identify the SV40 enhancer as a downstream target for signal transduction pathways in which p62 participates.
Rachubinski
R A
RA
Department of Cell Biology, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.
Marcus
S L
SL
Capone
J P
JP
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D019556:COS Cells; D002352:Carrier Proteins / Q000494:pharmacology*; D004742:Enhancer Elements, Genetic; D006801:Humans; D017874:Immediate-Early Proteins / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D011506:Proteins; D000071456:Sequestosome-1 Protein; D013539:Simian virus 40 / Q000235:genetics*; D013329:Structure-Activity Relationship; D051758:Transcription Factor TFIIH; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000187:drug effects*; D015533:Transcriptional Activation
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C490981:Gtf2h1 protein, mouse; D017874:Immediate-Early Proteins; D011506:Proteins; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D014157:Transcription Factors; D051758:Transcription Factor TFIIH