PMID- 23175187
OWN - NLM
STAT- MEDLINE
DCOM- 20130815
LR  - 20211021
IS  - 1476-5403 (Electronic)
IS  - 1350-9047 (Print)
IS  - 1350-9047 (Linking)
VI  - 20
IP  - 3
DP  - 2013 Mar
TI  - TLR2-dependent selective autophagy regulates NF-kappaB lysosomal degradation in 
      hepatoma-derived M2 macrophage differentiation.
PG  - 515-23
LID - 10.1038/cdd.2012.146 [doi]
AB  - Autophagy is a lysosomal pathway for cellular homeostasis control. Both 
      non-selective bulk autophagy and selective autophagy of specific proteins or 
      organelles have been found. Selective autophagy prevents cells from pathogen 
      invasion and stress damage, but its role in regulating transcriptional factors is 
      not clear. Using a macrophage cell differentiation model, the role of autophagy 
      in nuclear factor-kappaB (NF-kappaB) regulation is investigated. The bone marrow-derived 
      macrophages (BMDMs) will differentiate into a M2-like phenotype in the presence 
      of hepatoma tumor cell condition medium (CM). The TLR2 signaling drives this M2 
      polarization and causes NF-kappaB p65 degradation via lysosome-dependent pathway. The 
      CM-induced ubiquitinated- NF-kappaB p65 forms aggresome-like structures (ALS) in the 
      cytoplasm of cultured and hepatoma-associated M2 macrophages. This NF-kappaB 
      p65-contained ALS is recognized by p62/SQSTM1 and degraded by selective 
      autophagy. Treatment with the lysosomal inhibitor bafilomycin A1 or the knockdown 
      of Atg5 can prevent CM-induced NK-kappaB p65 degradation and induce M2 macrophages to 
      produce a high level of pro-inflammatory cytokines. Furthermore, TLR2 signal 
      induces sustained phosphorylation of extracellular signal-regulated kinase 1/2 to 
      facilitate this autophagy-dependent NF-kappaB regulation. Our finding provides a 
      novel pathway of NF-kappaB regulation by p62/SQSTM1-mediated selective autophagy.
FAU - Chang, C-P
AU  - Chang CP
AD  - Department of Microbiology and Immunology, College of Medicine, National Cheng 
      Kung University, Tainan, Taiwan, Republic of China. cpchang@mail.ncku.edu.tw
FAU - Su, Y-C
AU  - Su YC
FAU - Hu, C-W
AU  - Hu CW
FAU - Lei, H-Y
AU  - Lei HY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121123
PL  - England
TA  - Cell Death Differ
JT  - Cell death and differentiation
JID - 9437445
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Atg5 protein, mouse)
RN  - 0 (Autophagy-Related Protein 5)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Cytokines)
RN  - 0 (Macrolides)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (SQSTM1 protein, human)
RN  - 0 (Sequestosome-1 Protein)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Transcription Factor RelA)
RN  - 88899-55-2 (bafilomycin A1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/antagonists & inhibitors/genetics/metabolism
MH  - Animals
MH  - *Autophagy
MH  - Autophagy-Related Protein 5
MH  - Bone Marrow Cells/cytology
MH  - Carcinoma, Hepatocellular/metabolism
MH  - Cell Differentiation
MH  - Cell Line, Tumor
MH  - Culture Media, Conditioned/pharmacology
MH  - Cytokines/metabolism
MH  - Female
MH  - Lysosomes/drug effects/*metabolism
MH  - Macrolides/pharmacology
MH  - Macrophages/*cytology/drug effects/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Knockout
MH  - Microtubule-Associated Proteins/antagonists & inhibitors/genetics/metabolism
MH  - Mitogen-Activated Protein Kinase 1/metabolism
MH  - Mitogen-Activated Protein Kinase 3/metabolism
MH  - Phosphorylation
MH  - RNA Interference
MH  - RNA, Small Interfering/metabolism
MH  - Sequestosome-1 Protein
MH  - Toll-Like Receptor 2/*metabolism
MH  - Transcription Factor RelA/*metabolism
PMC - PMC3569990
EDAT- 2012/11/24 06:00
MHDA- 2013/08/16 06:00
PMCR- 2014/03/01
CRDT- 2012/11/24 06:00
PHST- 2012/11/24 06:00 [entrez]
PHST- 2012/11/24 06:00 [pubmed]
PHST- 2013/08/16 06:00 [medline]
PHST- 2014/03/01 00:00 [pmc-release]
AID - cdd2012146 [pii]
AID - 10.1038/cdd.2012.146 [doi]
PST - ppublish
SO  - Cell Death Differ. 2013 Mar;20(3):515-23. doi: 10.1038/cdd.2012.146. Epub 2012 
      Nov 23.