Hepatopoietin interacts directly with COP9 signalosome and regulates AP-1 activity.
Hepatopoietin (HPO)/augmenter of liver regeneration (ALR) is a specific hepatotrophic growth factor, which plays a key role in liver regeneration. Our previous study indicated that HPO executes its function by an inter-reactive network of the autocrine, paracrine and endocrine pathways. Recently, we have demonstrated that intracellular HPO interacts with Jun activation domain-binding protein 1 (JAB1) and leads to potentiation of activating protein-1 (AP-1) activity in a MAPK independent fashion. JAB1 is the fifth subunit of the COP9 signalosome (CSN), which is first identified as a suppressor of plant morphogenesis. A protein complex kinase activity associated with the CSN has been reported but not identified yet. In this report, we investigated further the association of HPO with the whole CSN. HPO exists in a complex with the eight-component CSN, both when purified from glycerol gradient centrifugation and when reciprocal immunoprecipitated from the lysates of transfected COS-7 cells. Intracellular HPO colocalizes with endogenous CSN in nucleus of hepatic cells. In addition, intracellular function of HPO that increases the phosphorylation of c-Jun leading to potentiate the AP-1 activity is inhibited by curcumin, a potent inhibitor of CSN-associated kinase. Taken together, these results elucidate a novel relationship of intracellular growth factor, HPO with large protein complex, CSN, which suggests a possible linkage between CSN and liver regeneration.
Department of Genomics and Proteomics, Beijing Institute of Radiation Medicine, Chinese National Human Genome Center, 27 Taiping Road, Beijing 100850, PR China.
Yan
Y
Wang
Chengrong
C
Lu
Handong
H
Wei
Na
N
Wang
Xiaoxiao
X
Chen
Lingqiang
L
Zhang
Yun
Y
Zhai
Yunping
Y
Zhu
Yinglin
Y
Lu
Fuchu
F
He
D000818:Animals; D000075686:COP9 Signalosome Complex; D019556:COS Cells; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000378:metabolism; D017930:Genes, Reporter; D016298:Hematopoietic Cell Growth Factors / Q000378:metabolism*; D007700:Kinetics; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D046912:Multiprotein Complexes; D010447:Peptide Hydrolases; D011506:Proteins / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection
D004268:DNA-Binding Proteins; D016298:Hematopoietic Cell Growth Factors; D046912:Multiprotein Complexes; D011506:Proteins; D011994:Recombinant Proteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D020928:Mitogen-Activated Protein Kinases; D010447:Peptide Hydrolases; D000075686:COP9 Signalosome Complex