Critical Role of Tyrosine 277 in the Ligand-Binding and Transactivating Properties of Retinoic Acid Receptor α†

Biochemistry ◽  
2000 ◽  
Vol 39 (9) ◽  
pp. 2183-2192 ◽  
Author(s):  
Sandrine Mailfait ◽  
Denise Belaiche ◽  
Mostafa Kouach ◽  
Nathalie Dallery ◽  
Philippe Chavatte ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Ligand Binding ◽  
Retinoic Acid Receptor ◽  
Critical Role ◽  
Acid Receptor ◽  
Retinoic Acid Receptor Α

scholarly journals Critical Role of Tyrosine 277 in the Ligand-Binding and Transactivating Properties of Retinoic Acid Receptor α

Biochemistry ◽  
2000 ◽  
Vol 39 (18) ◽  
pp. 5622-5622
Author(s):  
Sandrine Mailfait ◽  
Denise Belaiche ◽  
Mostafa Kouach ◽  
Nathalie Dallery ◽  
Philippe Chavatte ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Ligand Binding ◽  
Retinoic Acid Receptor ◽  
Critical Role ◽  
Acid Receptor ◽  
Retinoic Acid Receptor Α

Promyelocytic Leukemia-Retinoic Acid Receptor α Binds and Prevents Activation of the Fas Receptor and Suppresses Fas-Mediated Apoptosis.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3976-3976
Author(s):  
Rong-Hua Tao ◽  
Zuzana Berkova ◽  
Jillian Wise ◽  
Urszula Daniluk ◽  
Felipe Samaniego
Keyword(s):  
Retinoic Acid ◽  
Cancer Cells ◽  
Retinoic Acid Receptor ◽  
Critical Role ◽  
Death Receptor ◽  
Promyelocytic Leukemia ◽  
Attractive Potential ◽  
Acid Receptor ◽  
Nb4 Cells ◽  
Retinoic Acid Receptor Α

Abstract Abstract 3976 Poster Board III-912 Fas plays a critical role in cell proliferation and in the selective killing of autoreactive lymphocytes and abnormal cells, including infected cells. To explain the common expression of Fas and the resistance to the Fas killing observed in some normal and cancer cells, we have screened cells for potential regulators of the Fas death receptor. By using mass spectroscopy analysis of Fas-associated proteins, we identified a group of peptides derived from promyelocytic leukemia (PML). PML enhances pro-apoptotic signaling, while the promyelocytic leukemia–retinoic acid receptor α (PMLRARα) activates pro-survival pathways. Given these opposing functions, we tested whether PMLRARα, which typically operates in a dominant-negative manner, blocks Fas-mediated apoptosis. Co-immunoprecipitation analysis demonstrated that PMLRARα interacts with Fas in acute promyelocytic leukemia (APL)-derived NB4 cells, U937-PR9 cells and in APL primary cells. The binding of PMLRARα to Fas was mapped to the B-box domain of PMLRARα. Flow cytometry analysis of propidium iodide-stained and Annexin-V-stained cells challenged with Fas ligand (FasL) or agonistic anti-Fas antibody (CH-11) indicated that the presence of PMLRARα was associated with blocked Fas-mediated apoptosis at early and late stages. The knockdown of PMLRARα with shRNA sensitized the NB4 cells to Fas-mediated apoptosis. Expression of PMLRARα in U937-PR9 cells prevented Fas-mediated cleavage of procaspase-8 and also prevented procaspase-8 from binding to the Fas complex upon stimulation with the agonistic anti-Fas antibody (CH-11). Further analysis indicated that PMLRARα bound to FLIPL/S and forms an apoptotic inhibitory complex with Fas, which prevents Fas activation. The data suggest that tissue-specific inhibitors of Fas such as PMLRARα block Fas-mediated apoptosis and thus can contribute to cancer development. Our results may provide an explanation for the long-known role of PMLRARα and PML in the regulation of Fas signaling, which we have shown to occur by direct regulation. We have identified an attractive potential target to the regulation of apoptosis at the PMLRARα-Fas and PML-Fas interfaces. By neutralizing the effect of death receptor inhibitors such as PMLRARα and other potential inhibitors, we can improve on the success of the many chemotherapeutic treatments that depend on activation of death receptors for effective elimination of cancer cells. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Role of the retinoic acid receptor-α in HIV-associated nephropathy

2011 ◽  
Vol 79 (6) ◽  
pp. 624-634 ◽  
Author(s):  
Krishna K. Ratnam ◽  
Xiaobei Feng ◽  
Peter Y. Chuang ◽  
Vikram Verma ◽  
Ting-Chi Lu ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Retinoic Acid Receptor ◽  
Acid Receptor ◽  
Retinoic Acid Receptor Α

Cellular Retinoic Acid Bioavailability Determines Epithelial Integrity: Role of Retinoic Acid Receptor α Agonists in Colitis

2006 ◽  
Vol 71 (1) ◽  
pp. 250-258 ◽  
Author(s):  
Makoto Osanai ◽  
Nami Nishikiori ◽  
Masaki Murata ◽  
Hideki Chiba ◽  
Takashi Kojima ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Retinoic Acid Receptor ◽  
Epithelial Integrity ◽  
Acid Receptor ◽  
Retinoic Acid Receptor Α
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