Warning: Undefined array key "mm" in /www/wwwroot/www.ai-bt.com/si.php on line 10 Deprecated: trim(): Passing null to parameter #1 ($string) of type string is deprecated in /www/wwwroot/www.ai-bt.com/si.php on line 10 Interaction with RXR is necessary for NPM-RAR-induced myeloid differentiation blockade.

Literature DB >> 24183235

Interaction with RXR is necessary for NPM-RAR-induced myeloid differentiation blockade.

Elizabeth A Rush¹, Sheri L Pollock, Irina Abecassis, Robert L Redner.

Abstract

The t(5;17)(q35;q21) APL variant results in expression of a fusion protein linking the N-terminus of nucleophosmin (NPM) to the C-terminus of the retinoic acid receptor alpha (RAR). We have previously shown that NPM-RAR is capable of binding to DNA either as a homodimer or heterodimer with RXR. To determine the biological significance of NPM-RAR/RXR interaction, we developed two mutants of NPM-RAR that showed markedly diminished ability to bind RXR. U937 subclones expressing the NPM-RAR mutants showed significantly less inhibition of vitamin D3/TGFbeta-induced differentiation, compared with NPM-RAR. These results support the hypothesis that RXR interaction is necessary for NPM-RAR-mediated myeloid maturation arrest.

Entities: CellLine Chemical Disease Gene Mutation Species

Keywords: Acute promyelocytic leukemia; Differentiation; NPM-RAR; RXR

Mesh：

Substances：

Year: 2013 PMID： 24183235 PMCID： PMC3876950 DOI： 10.1016/j.leukres.2013.09.024

Source DB: PubMed Journal: Leuk Res ISSN： 0145-2126 Impact factor: 3.156

48 in total

1. Differentiation of t(5;17) variant acute promyelocytic leukemic blasts by all-trans retinoic acid.

Authors: R L Redner; S J Corey; E A Rush
Journal: Leukemia Date: 1997-07 Impact factor: 11.528

2. Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma.

Authors: S W Morris; M N Kirstein; M B Valentine; K Dittmer; D N Shapiro; A T Look; D L Saltman
Journal: Science Date: 1995-01-20 Impact factor: 47.728

3. Fusion proteins of the retinoic acid receptor-alpha recruit histone deacetylase in promyelocytic leukaemia.

Authors: F Grignani; S De Matteis; C Nervi; L Tomassoni; V Gelmetti; M Cioce; M Fanelli; M Ruthardt; F F Ferrara; I Zamir; C Seiser; F Grignani; M A Lazar; S Minucci; P G Pelicci
Journal: Nature Date: 1998-02-19 Impact factor: 49.962

4. Role of the histone deacetylase complex in acute promyelocytic leukaemia.

Authors: R J Lin; L Nagy; S Inoue; W Shao; W H Miller; R M Evans
Journal: Nature Date: 1998-02-19 Impact factor: 49.962

5. A transcriptional co-repressor that interacts with nuclear hormone receptors.

Authors: J D Chen; R M Evans
Journal: Nature Date: 1995-10-05 Impact factor: 49.962

6. A novel macromolecular structure is a target of the promyelocyte-retinoic acid receptor oncoprotein.

Authors: J A Dyck; G G Maul; W H Miller; J D Chen; A Kakizuka; R M Evans
Journal: Cell Date: 1994-01-28 Impact factor: 41.582

7. Nuclear receptor repression mediated by a complex containing SMRT, mSin3A, and histone deacetylase.

Authors: L Nagy; H Y Kao; D Chakravarti; R J Lin; C A Hassig; D E Ayer; S L Schreiber; R M Evans
Journal: Cell Date: 1997-05-02 Impact factor: 41.582

8. Fusion of retinoic acid receptor alpha to NuMA, the nuclear mitotic apparatus protein, by a variant translocation in acute promyelocytic leukaemia.

Authors: R A Wells; C Catzavelos; S Kamel-Reid
Journal: Nat Genet Date: 1997-09 Impact factor: 38.330

Interaction with RXR is necessary for NPM-RAR-induced myeloid differentiation blockade.

1. Differentiation of t(5;17) variant acute promyelocytic leukemic blasts by all-trans retinoic acid.

2. Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma.

3. Fusion proteins of the retinoic acid receptor-alpha recruit histone deacetylase in promyelocytic leukaemia.

4. Role of the histone deacetylase complex in acute promyelocytic leukaemia.

5. A transcriptional co-repressor that interacts with nuclear hormone receptors.

6. A novel macromolecular structure is a target of the promyelocyte-retinoic acid receptor oncoprotein.

7. Nuclear receptor repression mediated by a complex containing SMRT, mSin3A, and histone deacetylase.

8. Fusion of retinoic acid receptor alpha to NuMA, the nuclear mitotic apparatus protein, by a variant translocation in acute promyelocytic leukaemia.

9. The t(5;17) variant of acute promyelocytic leukemia expresses a nucleophosmin-retinoic acid receptor fusion.

10. The t(3;5)(q25.1;q34) of myelodysplastic syndrome and acute myeloid leukemia produces a novel fusion gene, NPM-MLF1.

1. The leukemic oncoprotein NPM1-RARA inhibits TP53 activity.

2. LG-362B targets PML-RARα and blocks ATRA resistance of acute promyelocytic leukemia.

3. NPM-RAR binding to TRADD selectively inhibits caspase activation, while allowing activation of NFκB and JNK.

4. Extrinsic apoptosis is impeded by direct binding of the APL fusion protein NPM-RAR to TRADD.