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Hepatopoietin interacts directly with COP9 signalosome and regulates AP‐1 activity
Author(s) -
Wang Yan,
Lu Chengrong,
Wei Handong,
Wang Na,
Chen Xiaoxiao,
Zhang Lingqiang,
Zhai Yun,
Zhu Yunping,
Lu Yinglin,
He Fuchu
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2004.07.012
Subject(s) - cop9 signalosome , microbiology and biotechnology , chemistry , biology , biochemistry , peptide hydrolases , protease , enzyme
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.