Document Detail


PMLRARα binds to Fas and suppresses Fas-mediated apoptosis through recruiting c-FLIP in vivo.
MedLine Citation:
PMID:  21803845     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Defective Fas signaling leads to resistance to various anticancer therapies. Presence of potential inhibitors of Fas which could block Fas signaling can explain cancer cells resistance to apoptosis. We identified promyelocytic leukemia protein (PML) as a Fas-interacting protein using mass spectrometry analysis. The function of PML is blocked by its dominant-negative form PML-retinoic acid receptor α (PMLRARα). We found PMLRARα interaction with Fas in acute promyelocytic leukemia (APL)-derived cells and APL primary cells, and PML-Fas complexes in normal tissues. Binding of PMLRARα to Fas was mapped to the B-box domain of PML moiety and death domain of Fas. PMLRARα blockage of Fas apoptosis was demonstrated in U937/PR9 cells, human APL cells and transgenic mouse APL cells, in which PMLRARα recruited c-FLIP(L/S) and excluded procaspase 8 from Fas death signaling complex. PMLRARα expression in mice protected the mice against a lethal dose of agonistic anti-Fas antibody (P < .001) and the protected tissues contained Fas-PMLRARα-cFLIP complexes. Taken together, PMLRARα binds to Fas and blocks Fas-mediated apoptosis in APL by forming an apoptotic inhibitory complex with c-FLIP. The presence of PML-Fas complexes across different tissues implicates that PML functions in apoptosis regulation and tumor suppression are mediated by direct interaction with Fas.
Authors:
Rong-Hua Tao; Zuzana Berkova; Jillian F Wise; Abdol-Hossein Rezaeian; Urszula Daniluk; Xue Ao; David H Hawke; Judith E Karp; Hui-Kuan Lin; Jeffrey J Molldrem; Felipe Samaniego
Related Documents :
21057585 - Immune system and schizophrenia.
21893045 - Differential expression of co-signal molecules and migratory properties in four distinc...
12950415 - Review article: mechanisms of action of mesalazine in preventing colorectal carcinoma i...
17324565 - Macrolide antibiotics promote the lps-induced upregulation of prostaglandin e receptor ...
23412435 - Appearance of remodelled and dendritic cell-rich alveolar-lymphoid interfaces provides ...
19575365 - Repair-related activation of hedgehog signaling promotes cholangiocyte chemokine produc...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-07-29
Journal Detail:
Title:  Blood     Volume:  118     ISSN:  1528-0020     ISO Abbreviation:  Blood     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-09-16     Completed Date:  2011-11-21     Revised Date:  2013-08-27    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3107-18     Citation Subset:  AIM; IM    
Affiliation:
Departments of Lymphoma and Myeloma, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD95 / antagonists & inhibitors,  genetics,  metabolism*,  physiology
Apoptosis* / genetics
CASP8 and FADD-Like Apoptosis Regulating Protein / genetics,  metabolism*,  physiology
Cells, Cultured
Down-Regulation
Female
HL-60 Cells
Humans
Mice
Mice, Inbred C57BL
Mice, Transgenic
Models, Biological
Oncogene Proteins, Fusion / genetics,  metabolism*,  physiology
Protein Binding / physiology
U937 Cells
Grant Support
ID/Acronym/Agency:
5P30 CA06973-46/CA/NCI NIH HHS; CA1206173/CA/NCI NIH HHS; CA153170/CA/NCI NIH HHS; CA158692/CA/NCI NIH HHS; DK091490/DK/NIDDK NIH HHS; P50 CA100632/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD95; 0/CASP8 and FADD-Like Apoptosis Regulating Protein; 0/CFLAR protein, human; 0/FAS protein, human; 0/Oncogene Proteins, Fusion; 0/promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein
Comments/Corrections

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


Previous Document:  Vitamin, mineral, and specialty supplements and risk of hematologic malignancies in the prospective ...
Next Document:  CD63 is an essential cofactor to leukocyte recruitment by endothelial P-selectin.