Document Detail


Phospholipase Cβ1 is linked to RNA interference of specific genes through translin-associated factor X.
MedLine Citation:
PMID:  22889834     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Phospholipase Cβ1 (PLCβ1) is a G-protein-regulated enzyme whose activity results in proliferative and mitogenic changes in the cell. We have previously found that in solution PLCβ1 binds to the RNA processing protein translin-associated factor X (TRAX) with nanomolar affinity and that this binding competes with G proteins. Here, we show that endogenous PLCβ1 and TRAX interact in SK-N-SH cells and also in HEK293 cells induced to overexpress PLCβ1. In HEK293 cells, TRAX overexpression ablates Ca(2+) signals generated by G protein-PLCβ1 activation. TRAX plays a key role in down-regulation of proteins by small, interfering RNA, and PLCβ1 overexpression completely reverses the 2- to 4-fold down-regulation of GAPDH by siRNA in HEK293 and HeLa cells as seen by an ∼4-fold recovery in both the transcript and protein levels. Also, down-regulation of endogenous PLCβ1 in HEK293 and HeLa cells allows for an ∼20% increase in siRNA(GAPDH) silencing. While PLCβ1 overexpression results in a 50% reversal of cell death caused by siRNA(LDH), it does not affect cell survival or silencing of other genes (e.g., cyclophilin, Hsp90, translin). PLCβ1 overexpression in HEK293 and HeLa cells causes a 30% reduction in the total amount of small RNAs. LDH and GAPDH are part of a complex that promotes H2B synthesis that allows cells to progress through the S phase. We find that PLCβ1 reverses the cell death and completely rescues H2B levels caused by siRNA knockdown of LDH or GAPDH. Taken together, our study shows a novel role of PLCβ1 in gene regulation through TRAX association.
Authors:
Finly Philip; Yuanjian Guo; Omoz Aisiku; Suzanne Scarlata
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-08-13
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  26     ISSN:  1530-6860     ISO Abbreviation:  FASEB J.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-30     Completed Date:  2013-04-11     Revised Date:  2013-12-05    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4903-13     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Active Transport, Cell Nucleus
Blotting, Western
Cell Line, Tumor
Cell Nucleus / metabolism
DNA-Binding Proteins / genetics,  metabolism*
Fluorescence Resonance Energy Transfer
GTP-Binding Protein alpha Subunits, Gq-G11 / genetics,  metabolism
Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+) / genetics,  metabolism*
HEK293 Cells
HSP90 Heat-Shock Proteins / genetics,  metabolism
HeLa Cells
Histones / metabolism
Humans
L-Lactate Dehydrogenase / genetics,  metabolism*
Luminescent Proteins / genetics,  metabolism
Microscopy, Confocal
Phospholipase C beta / genetics,  metabolism*
Protein Binding
RNA Interference*
Transfection
Grant Support
ID/Acronym/Agency:
GM53132/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/DNA-Binding Proteins; 0/HSP90 Heat-Shock Proteins; 0/Histones; 0/Luminescent Proteins; 0/TSNAX protein, human; EC 1.1.1.27/L-Lactate Dehydrogenase; EC 1.2.1.9/Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+); EC 3.1.4.11/PLCB1 protein, human; EC 3.1.4.11/Phospholipase C beta; EC 3.6.5.1/GTP-Binding Protein alpha Subunits, Gq-G11
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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