Degradation of c-Fos protein expressed by N-methyl-d-aspartic acid in nuclear fractions of murine hippocampus

Manabe, Takayuki; Kuramoto, Nobuyuki; Nakamichi, Noritaka; Aramachi, Katsuhide; Baba, Katsuhiro; Hanabusa, Takao; Yoneyama, Mitsutoshi; Yoneda, Yukio

doi:10.1016/s0006-8993(01)02464-7

Cited by 11 publications

(7 citation statements)

References 29 publications

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“…Transcription factors whose functional activity is regulated at the level of their degradation include NFB (Desterro et al, 2000), c-Myc (Sears et al, 1999), and c-Fos (Ferrara et al, 2003), among others. In many instances, phosphorylation is a key regulator of the stability of a transcription factor, as has been shown for c-Fos Tsurumi et al, 1995), Fos-related antigen-1 (Fra-1) (Vial and Marshall, 2003), Fra-2 (Manabe et al, 2001), c-Jun (Fuchs et al, 1996), JunB (Fuchs et al, 1997), ATF2 (Fuchs et al, 2000), and p53 (Buschmann et al, 2001). Our studies thus add ⌬FosB to this list of transcription factors whose functional activity is regulated through its phosphorylated-dependent stability.…”

Section: Discussionmentioning

confidence: 96%

Regulation of ΔFosB Stability by Phosphorylation

Ulery¹,

Rudenko²,

Nestler³

2006

J. Neurosci.

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The transcription factor ⌬FosB (also referred to as FosB2 or FosB[short form]) is an important mediator of the long-term plasticity induced in brain by chronic exposure to several types of psychoactive stimuli, including drugs of abuse, stress, and electroconvulsive seizures. A distinct feature of ⌬FosB is that, once induced, it persists in brain for relatively long periods of time in the absence of further stimulation. The mechanisms underlying this apparent stability, however, have remained unknown. Here, we demonstrate that ⌬FosB is a relatively stable transcription factor, with a half-life of ϳ10 h in cell culture. Furthermore, we show that ⌬FosB is a phosphoprotein in brain and that phosphorylation of a highly conserved serine residue (Ser27) in ⌬FosB protects it from proteasomal degradation. We provide several lines of evidence suggesting that this phosphorylation is mediated by casein kinase 2. These findings constitute the first evidence that ⌬FosB is phosphorylated and demonstrate that phosphorylation contributes to its stability, which is at the core of its ability to mediate long-lasting adaptations in brain.

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Section: Discussionmentioning

confidence: 96%

Regulation of ΔFosB Stability by Phosphorylation

Ulery¹,

Rudenko²,

Nestler³

2006

J. Neurosci.

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“…Although the present study does not deal with expression of these proteins after exposure to NMDA, there is emerging evidence for expression of the c‐ fos gene as well as the c‐Fos protein in vitro through activation of NMDA receptor, as described above. The systemic administration of NMDA results in transient expression of c‐Fos and Fra‐2 proteins in murine hippocampus in vivo (Manabe et al, 2001). Identification of family member proteins is undoubtedly crucial for elucidation of molecular mechanisms underlying consolidation of transient extracellular NMDA signals but is beyond the scope of the present study, which focuses on the search for the origin of intracellular free Ca 2+ ions required for the potentiation after brief exposure to NMDA.…”

Section: Discussionmentioning

confidence: 99%

“…Hippocampal preparations cultured for 3, 5, and 9 DIV were collected in homogenizing buffer [20 mM Tris‐HCl buffer (pH 7.5) containing 1 mM EDTA, 1 mM EGTA, 10 mM NaF, 10 mM sodium β‐glycerophosphate (NaGP), 10 mM sodium pyrophosphate, 1 mM sodium orthovanadate, and 1 μg/ml of various protease inhibitors [( p ‐amidinophenyl)methanesulfonyl fluoride, leupeptin, antipain, and benzamidine], as described elsewhere (Manabe et al, 2001). Buffer and other solutions used in this study were all sterilized before each use by filtration though a nitrocellulose membrane filter with a pore size of 0.22 μm to avoid possible microbial contamination (Yoneda and Ogita, 1989).…”

Section: Methodsmentioning

confidence: 99%

Potentiation of nuclear activator protein‐1 DNA binding following brief exposure to N‐methyl‐D‐aspartate in immature cultured rat hippocampal neurons

Hanabusa

Kuramoto

Maruyama

et al. 2002

J of Neuroscience Research

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Similar potentiation was seen with the nuclear transcription factor activator protein-1 (AP1) binding in rat hippocampal neurons cultured for 3 and 9 DIV, when determined immediately after exposure to 500 microM N-methyl-D-aspartate (NMDA) for 60-120 min. Growth-associated protein-43 was markedly expressed in hippocampal neurons cultured for 3-5 DIV, with a decline up to 9 DIV. In immature neurons cultured for 3 DIV, NMDA was effective in significantly potentiating AP1 binding even in the presence of Mg(2+) with less potency than in the absence of Mg(2+) when determined immediately after sustained exposure for 120 min. When determined 120 min after brief exposure for 5 min, by contrast, NMDA significantly potentiated AP1 binding at a range of 100-500 microM only in the absence of Mg(2+) in immature neurons cultured for 3 DIV. At least 60 min was required for significant potentiation of AP1 binding as an interval between brief exposure and subsequent cell harvest. Dizocilpine abolished the potentiation determined 120 min after brief exposure to 500 microM NMDA, and both dantrolene and nifedipine were similarly effective in significantly preventing the potentiation at 10-50 microM. These results suggest that NMDA may potentiate AP1 binding following a sustained increase in intracellular free Ca(2+) concentrations through influxes across NMDA-operated and L-type voltage-sensitive Ca(2+) channels, in addition to release from intracellular Ca(2+) stores, in immature cultured rat hippocampal neurons.

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“…Immunoblotting was performed as previously described 42,43 with minor modifications. Anti-HMGA1 (HMG-I(Y) (N-19)) and anti-U1-70K (U1 SnRNP 70 (C-18)) goat polyclonal antibodies were purchased (Santa Cruz Biotechnology).…”

Section: Immunoblotting Assaysmentioning

confidence: 99%

Induced HMGA1a expression causes aberrant splicing of Presenilin-2 pre-mRNA in sporadic Alzheimer's disease

et al. 2003

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The aberrant splicing isoform (PS2V), generated by exon 5 skipping of the Presenilin-2 (PS2) gene transcript, is a diagnostic feature of sporadic Alzheimer's disease (AD). We found PS2V is hypoxia-inducible in human neuroblastoma SK-N-SH cells. We purified a responsible trans-acting factor based on its binding to an exon 5 fragment. The factor was identified as the high mobility group A1a protein (HMGA1a; formerly HMG-I). HMGA1a bound to a specific sequence on exon 5, located upstream of the 5 0 splice site. HMGA1a expression was induced by hypoxia and the protein was accumulated in the nuclear speckles with the endogenous splicing factor SC35. Overexpression of HMGA1a generated PS2V, but PS2V was repressed by cotransfection with the U1 snRNP 70K protein that has a strong affinity to HMGA1a. HMGA1a could interfere with U1 snRNP binding to the 5 0 splice site and caused exon 5 skipping. HMGA1a levels were significantly increased in the brain tissue from sporadic AD patients. We propose a novel mechanism of sporadic AD that involves HMGA1a-induced aberrant splicing of PS2 premRNA in the absence of any mutations.

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Degradation of c-Fos protein expressed by N-methyl-d-aspartic acid in nuclear fractions of murine hippocampus

Cited by 11 publications

References 29 publications

Regulation of ΔFosB Stability by Phosphorylation

Regulation of ΔFosB Stability by Phosphorylation

Potentiation of nuclear activator protein‐1 DNA binding following brief exposure to N‐methyl‐D‐aspartate in immature cultured rat hippocampal neurons

Induced HMGA1a expression causes aberrant splicing of Presenilin-2 pre-mRNA in sporadic Alzheimer's disease

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