[Comparative study of two fusion retinoic acid receptor alpha in acute promyelocytic leukemia].
OBJECTIVE
To make a comparison of biological properties between PML-RARalpha and PLZF-RARalpha fusion proteins.


METHODS
Receptor radioligand binding assay, receptor DNA binding assay and immunofluorescence methods were used.


CONCLUSIONS
PML-RARalpha and PLZF-RARalpha had similar ligand-binding affinities. Both could bind in vitro to retinoic acid response elements (RAREs) forming homodimers and to retinoic acid X receptor. However ,they differed in the relative binding affinities to different RAREs,the behavior of forming complex with RXR and the subcellular localization. More importantly, PML-RARalpha and PLZF-RARalpha could block different regulatory pathways mediated by PML or PLZF, through heterocomplex formation with wild-type PML or PLZF. The differences between PML-RARalpha and PLZF-RARalpha may in part explain the apparent resistance of APL with t(11;17) to differentiating effect of all-trans retinoic acid (ATRA).
Zhong
H
H
Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025.
Dong
S
S
Chen
G
G
Jiang
X
X
Xia
Z
Z
Yi
N
N
Wang
Z
Z
Chen
S
S
Xu
Y
Y
Chen
L
L
D004247:DNA / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D021381:Protein Transport; D011869:Radioligand Assay; D018168:Receptors, Retinoic Acid / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D000072482:Retinoic Acid Receptor alpha; D014162:Transfection
C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D011993:Recombinant Fusion Proteins; D000072482:Retinoic Acid Receptor alpha; D004247:DNA