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Chemical Genetic Identification of the IGF-linked Pathway That Is Mediated by STAT6 and MFP2

Chemical Genetic Identification of the IGF-linked Pathway That Is Mediated by STAT6 and MFP2

Yongmun Choi, Hiroki Shimogawa, Koji Murakami, Latha Ramdas, Wei Zhang, Jun Qin, Motonari Uesugi

Chem Biol. 2006 Mar;13(3):241-9.

PMID: 16638529

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP331859860	Chromeceptin		331859-86-0	Price

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