Abstract:
:We previously identified a nuclear envelope protein repressor element-1 silencing transcription factor (REST)/neuron-restrictive silencer factor (NRSF)-interacting Lin-11, Isl-1 and Mec-3 (LIM) domain protein (RILP) that we proposed functions in the nuclear translocation of the transcriptional repressor REST/NRSF. In this study we assessed the functionality of the prenylation motif, protein kinase A (PKA) phosphorylation sites and nuclear localization sequences (NLSs) of RILP. [(3)H]-mevalonolactone labeled endogenous RILP, showing that RILP is indeed prenylated, while phosphorylation analysis showed that the two PKA sites are phosphorylated. Blocking RILP prenylation, mutating the NLSs or mutating the PKA phosphorylation sites caused RILP to mislocalize to the cytosol. Concurrent with this mislocalization of RILP, REST/NRSF and REST4, which are normally found in the nucleus, co-localized in the cytosol with the RILP mutants. This provides additional evidence that RILP interacts with REST/NRSF and REST4 in vivo, and is involved in the nuclear localization of REST/NRSF and REST4. Reporter gene analysis using the promoter region of the human cholinergic gene locus revealed that these RILP mutants prevented repression of the reporter gene. By trapping REST/NRSF in the cytosol, the RILP mutants prevented translocation to the nucleus where REST/NRSF binds to an RE-1/NRSE element to repress gene transcription. These results show that RILP is required for REST/NRSF nuclear targeting and function.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Shimojo M,Hersh LBdoi
10.1111/j.1471-4159.2005.03608.xkeywords:
subject
Has Abstractpub_date
2006-02-01 00:00:00pages
1130-8issue
4eissn
0022-3042issn
1471-4159pii
JNC3608journal_volume
96pub_type
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journal_title:Journal of neurochemistry
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pub_type: 杂志文章
doi:10.1111/j.1471-4159.1984.tb05398.x
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journal_title:Journal of neurochemistry
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abstract:UNLABELLED:J. Neurochem. (2012) 121, 597-606. ABSTRACT:In cultured rat neocortical interneurons, we have studied the effect of long-term application of NMDA or AMPA on the surface density of the NMDA (GluN) receptor subunits GluN1 and GluN2B. Stimulation of Ca(2+) -permeable AMPA (GluA) receptors located on the intern...
journal_title:Journal of neurochemistry
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更新日期:2012-05-01 00:00:00
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journal_title:Journal of neurochemistry
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更新日期:2000-11-01 00:00:00
abstract::Tissue plasminogen activator (tPA) administration beyond 4.5 h of stroke symptoms is beneficial for patients but has an increased risk of cerebral hemorrhage. Thus, increasing the therapeutic window of tPA is important for stroke recovery. We previously showed that prothymosin alpha (ProTα) or its mimetic hexapeptide ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.14858
更新日期:2020-06-01 00:00:00