Regulation of the Neuronal Fate by ΔFosB and its Downstream Target, Galectin-1

Author(s): Tomofumi Miura, Yoshinori Ohnishi, Hideaki Kurushima, Hidenori Horie, Toshihiko Kadoya, Yusaku Nakabeppu.

Journal Name: Current Drug Targets

Volume 6 , Issue 4 , 2005

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Abstract:

In mammals, the regulation of the cell fate to either proliferate, differentiate, arrest cell growth, or initiate programmed cell death is the most fundamental mechanism for maintaining normal cell function and tissue homeostasis. Under multiple signaling pathways, Jun and Fos family proteins are known to play important roles as components of an AP-1 (activator protein-1) complex, to regulate the transcription of various genes involved in cell proliferation, differentiation and programmed cell death. ΔFosB, one of the AP-1 subunits encoded by alternatively spliced fosB mRNA, triggers one round of proliferation in quiescent rat embryo cell lines, followed by a different cell fate such as morphological alteration or delayed cell death. As one of the downstream targets of the ΔFosB in rat3Y1 cell line, we identified rat galectin-1 and its novel variant, galectin-1β, and demonstrated that the expression of galectin-1 is required for the proliferative activation of quiescent rat1A cells by ΔFosB, thus indicating that galectin-1 is one of functional targets of ΔFosB. The expression of ΔFosB is highly inducible in the adult brain in response to various insults such as ischemic reperfusion injury, seizure induced by electric stimulation or cocaine administration. On the other hand, galectin- 1 has also been shown to be involved in the regeneration of damaged axons in the peripheral nerve, as well as in neurite outgrowth or synaptic connectivity in the olfactory system during development. We herein propose that ΔFosB together with galectin-1, may therefore mediate neuroprotection and neurogenesis in response to brain damage.

Keywords: alternative splicing, FosB, galectin, redox regulation, cell fate, neuronal fate

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Article Details

VOLUME: 6
ISSUE: 4
Year: 2005
Page: [437 - 444]
Pages: 8
DOI: 10.2174/1389450054021963
Price: $58

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