p38JAB1 binds to the intracellular precursor of the lutropin/choriogonadotropin receptor and promotes its degradation.
Using the C-terminal tail of the rat lutropin/choriogonadotropin receptor (rLHR) as "bait" in a yeast two-hybrid screen resulted in the identification of p38(JAB1) (a protein initially identified as a co-activator of c-Jun) as a putative rLHR binding partner. More recently p38(JAB1) has been shown to promote the degradation of a cyclin-dependent kinase inhibitor and to be a component of the COP9 signalosome. Microscopic localization of an epitope-tagged p38(JAB1) expressed in 293 cells revealed a punctuated perinuclear and cytosolic localization, while cell fractionation studies showed that most of the p38(JAB1) was in a high speed supernatant. Co-transfection of 293 cells revealed that p38(JAB1) binds to the immature 68-kDa precursor of the rLHR that resides in the endoplasmic reticulum and promotes its degradation. It does not appear to interact with the cell surface rLHR, however, and it does not affect its expression. When transfected into HeLa cells, p38(JAB1) potentiates the transcriptional activity of c-Jun, but co-transfection with rLHR prevents this effect. We conclude that p38(JAB1) interacts with the rLHR precursor and promotes its degradation. These results reveal a novel protein binding partner of the rLHR and are consistent with current views of the functions of p38(JAB1).
Li
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Department of Pharmacology, University of Iowa College of Medicine, Iowa City, Iowa 52242-1109, USA.
Liu
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Ascoli
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D000595:Amino Acid Sequence; D000818:Animals; D000075686:COP9 Signalosome Complex; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D010447:Peptide Hydrolases; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011974:Receptors, LH / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011498:Protein Precursors; D011974:Receptors, LH; D014157:Transcription Factors; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; D000075686:COP9 Signalosome Complex