2006年3月
Chemical genetic identification of the IGF-linked pathway that is mediated by STAT6 and MFP2
CHEMISTRY & BIOLOGY
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- 巻
- 13
- 号
- 3
- 開始ページ
- 241
- 終了ページ
- 249
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.chembiol.2005.12.011
- 出版者・発行元
- CELL PRESS
Insulin-like growth factor 2 (IGF2) is a potent mitogen whose deregulation plays a role in developing liver, breast, and prostate cancers. Here, we take a small-molecule approach to investigate molecular pathways that modulate IGF2 signaling, by using chromeceptin, a synthetic molecule that selectively impairs the viability and growth of IGF2-overexpressing hepatocellular carcinoma cells. Affinity purification revealed that chromeceptin binds to multifunctional protein 2 (MFP-2), a seemingly multifunctional enzyme implicated in peroxisomal beta-oxidation. The small molecule-protein interaction stimulates the expression of IGF binding protein 1 (IGFBP-1) and suppressor of cytokine signaling-3 (SOCS-3), two cellular attenuators of the IGF signals, through activation of signal transducers and activators of transcription 6 (STAT6). The results underline the importance of STATs in IGF/insulin regulation, and they implicate a new pathway for STAT6 activation that is amenable to small-molecule intervention.
- リンク情報
- ID情報
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- DOI : 10.1016/j.chembiol.2005.12.011
- ISSN : 1074-5521
- PubMed ID : 16638529
- Web of Science ID : WOS:000236482100004