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FOSB Proteins (fosb + protein)
Selected AbstractsHUMAN STUDY: FOSB proteins in the orbitofrontal and dorsolateral prefrontal cortices of human alcoholicsADDICTION BIOLOGY, Issue 3 2009Hiroyuki Watanabe ABSTRACT The transcription factor ,FosB is accumulated in the addiction circuitry, including the orbitofrontal and medial prefrontal cortices of rodents chronically exposed to ethanol or other drugs of abuse, and has been suggested to play a direct role in addiction maintenance. To address this hypothesis in the context of substance dependence in humans, we compared the immunoreactivities of FOSB proteins in the orbitofrontal and dorsolateral prefrontal cortices (OFC and DLPFC respectively) between controls and alcoholics using semiquantitative immunoblotting. In both structures, we detected three forms of FOSB, one of which was ,FOSB, but in neither case did their immunoreactivities differ between the groups. Our results indicate that the ,FOSB immunoreactivity in the human brain is very low, and that it is not accumulated in the OFC and DLPFC of human alcoholics, suggesting that it may not be directly involved in addiction maintenance, at least not in ethanol dependence. [source] Regulation of ,FosB transcriptional activity by Ser27 phosphorylationEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2007Paula G. Ulery Abstract The transcription factor, ,FosB, is an important mediator of the long-term plasticity induced in brain by chronic exposure to drugs of abuse, stress, or several other psychoactive stimuli. We have previously demonstrated that the casein kinase 2 (CK2)-mediated phosphorylation of a highly conserved N-terminal serine (Ser27) plays a critical role in regulating ,FosB's unusual stability, while it does not affect that of the full-length FosB protein. In the present study, we analysed whether CK2 and Ser27 phosphorylation also play a role in regulating ,FosB's transcriptional activity. Our findings indicate that CK2 activation increases ,FosB's transactivation potential, while CK2 inhibition decreases it. Further, we show that preventing Ser27 phosphorylation by mutating the site to Ala results in a significant decrease in ,FosB transactivation, without affecting ,FosB's subcellular localization or DNA-binding affinity. In contrast, Ser27 does not seem to play a role in the transactivation potential of full-length FosB. These findings constitute the first evidence of a role for phosphorylation in ,FosB's transcriptional activity. [source] Striatal regulation of ,FosB, FosB, and cFos during cocaine self-administration and withdrawalJOURNAL OF NEUROCHEMISTRY, Issue 1 2010Erin B. Larson J. Neurochem. (2010) 115, 112,122. Abstract Chronic drug exposure induces alterations in gene expression profiles that are thought to underlie the development of drug addiction. The present study examined regulation of the Fos-family of transcription factors, specifically cFos, FosB, and ,FosB, in striatal subregions during and after chronic intravenous cocaine administration in self-administering and yoked rats. We found that cFos, FosB, and ,FosB exhibit regionally and temporally distinct expression patterns, with greater accumulation of ,FosB protein in the nucleus accumbens (NAc) shell and core after chronic cocaine administration, whereas ,FosB increases in the caudate-putamen (CPu) remained similar with either acute or chronic administration. In contrast, tolerance developed to cocaine-induced mRNA for ,FosB in all three striatal subregions with chronic administration. Tolerance also developed to FosB expression, most notably in the NAc shell and CPu. Interestingly, tolerance to cocaine-induced cFos induction was dependent on volitional control of cocaine intake in ventral but not dorsal striatal regions, whereas regulation of FosB and ,FosB was similar in cocaine self-administering and yoked animals. Thus, ,FosB-mediated neuroadaptations in the CPu may occur earlier than previously thought with the initiation of intravenous cocaine use and, together with greater accumulation of ,FosB in the NAc, could contribute to addiction-related increases in cocaine-seeking behavior. [source] | ||||||||||