Document Detail

Raf/MEK/ERK can regulate cellular levels of LC3B and SQSTM1/p62 at expression levels.
MedLine Citation:
PMID:  25128814     Owner:  NLM     Status:  Publisher    
While cellular LC3B and SQSTM1 levels serve as key autophagy markers, their regulation by different signaling pathways requires better understanding. Here, we report the mechanisms by which the Raf/MEK/ERK pathway regulates cellular LC3B and SQSTM1 levels. In different cell types, ΔRaf-1:ER- or B-Raf(V600E)-mediated MEK/ERK activation increased LC3B-I, LC3B-II, and SQSTM1/p62 levels, which was accompanied by increased BiP/GRP78 expression. Use of the autophagy inhibitors chloroquine and bafilomycin A1, or RNA interference of ATG7, suggested that these increases in LC3B and SQSTM1 levels were in part attributed to altered autophagic flux. However, intriguingly, these increases were also attributed to their increased expression. Upon Raf/MEK/ERK activation, mRNA levels of LC3B and SQSTM1 were also increased, and subsequent luciferase reporter analyses suggested that SQSTM1 upregulation was mediated at transcription level. Under this condition, transcription of BiP/GRP78 was also increased, which was necessary for Raf/MEK/ERK to regulate LC3B at the protein, but not mRNA, level. This suggests that BiP has a role in regulating autophagy machinery when Raf/MEK/ERK is activated. In conclusion, these results suggest that, under a Raf/MEK/ERK-activated condition, the steady-state cellular levels of LC3B and SQSTM1 can also be determined by their altered expression wherein BiP is utilized as an effector of the signaling.
Jin-Hwan Kim; Seung-Keun Hong; Pui-Kei Wu; Alexsia L Richards; William T Jackson; Jong-In Park
Related Documents :
22433574 - A sigma-class glutathione s-transferase from solen grandis that responded to microorgan...
23830104 - Investigating host dependence of xylose utilization in recombinant saccharomyces cerevi...
10786614 - Primary structure, chromosomal mapping, expression and transcriptional activity of muri...
22133054 - Astrocyte elevated gene-1 (aeg-1) is a marker for aggressive salivary gland carcinoma.
11086064 - Tissue-specific expression of rat il-18 gene and response to adrenocorticotropic hormon...
23318274 - The human liver fatty acid binding protein (fabp1) gene is activated by foxa1 and pparα...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-8-13
Journal Detail:
Title:  Experimental cell research     Volume:  -     ISSN:  1090-2422     ISO Abbreviation:  Exp. Cell Res.     Publication Date:  2014 Aug 
Date Detail:
Created Date:  2014-8-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0373226     Medline TA:  Exp Cell Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014. Published by Elsevier Inc.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

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

Previous Document:  Mammalian aPKC/Par polarity complex mediated regulation of epithelial division orientation and cell ...
Next Document:  Hierarchical organization of fetal and adult hematopoietic stem cells.