The impact of differential binding of wild-type RARα, PML-, PLZF- and NPM-RARα fusion proteins towards transcriptional co-activator, RIP-140, on retinoic acid responses in acute promyelocytic leukemia

So, Chi Wai Eric; Dong, Shuang; So, Chi‐Chiu; Cheng, Guoxiang; Huang, Qiu-Hua; Chen, S. J.; Li, Chan

doi:10.1038/sj.leu.2401643

Cited by 28 publications

(39 citation statements)

References 44 publications

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“…This works in part by inducing the dissociation of transcriptional co-repressors from the fusion protein PML/RAR␣ and thereby releasing suppression of Sin3 and histone deacetylase from the transcriptional complex, allowing the cells to differentiate. 7 Another way in which transcriptional activation can be regulated is through ubiquitindependent proteolysis. 8 …”

Section: Transcription Factorsmentioning

confidence: 99%

“…248 Normally, RAR␣ can dimerize with retinoid X receptors (RXRs) in the enhancer/promoter region of specific target genes and activate transcription. 7 In the absence of ligand retinoic acid, basal transcription is repressed due to the association of RAR/RXR heterodimers with transcriptional corepressors. Transcriptional repressors and histone deacetylases are then recruited which result in the nearby chromatin being inaccessible to transcriptional activators and thus repress basal transcription.…”

Section: Pml/rar␣mentioning

confidence: 99%

“…Transcriptional repressors and histone deacetylases are then recruited which result in the nearby chromatin being inaccessible to transcriptional activators and thus repress basal transcription. 7 ATRA (all-trans retinoic acid) treatment causes the induction of dissociation of the co-repressor complex, recruitment of co-activators to the transcriptional complex, and activation of gene expression. 7 Both PML/RAR␣ and PLZF/RAR␣ are considered RAR mutants because of their ability to mimic this wild-type RAR␣ activity.…”

Section: Pml/rar␣mentioning

confidence: 99%

“…7 ATRA (all-trans retinoic acid) treatment causes the induction of dissociation of the co-repressor complex, recruitment of co-activators to the transcriptional complex, and activation of gene expression. 7 Both PML/RAR␣ and PLZF/RAR␣ are considered RAR mutants because of their ability to mimic this wild-type RAR␣ activity. [249][250][251] …”

Section: Pml/rar␣mentioning

confidence: 99%

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Transcription factors and translocations in lymphoid and myeloid leukemia

Crans¹,

Sakamoto²

2001

Leukemia

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Chromosomal translocations involving transcription factors and aberrant expression of transcription factors are frequently associated with leukemogenesis. Transcription factors are essential in maintaining the regulation of cell growth, development, and differentiation in the hematopoietic system. Alterations in the mechanisms that normally control these functions can lead to hematological malignancies. Further characterization of the molecular biology of leukemia will enhance our ability to develop disease-specific treatment strategies, and to develop effective methods of diagnosis and prognosis. Leukemia (2001) 15, 313-331.

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Section: Transcription Factorsmentioning

confidence: 99%

Section: Pml/rar␣mentioning

confidence: 99%

Section: Pml/rar␣mentioning

confidence: 99%

Section: Pml/rar␣mentioning

confidence: 99%

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Transcription factors and translocations in lymphoid and myeloid leukemia

Crans¹,

Sakamoto²

2001

Leukemia

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“…PLZFRARa/RXRa heterodimers bind to RAREs (retinoic acid response elements) with higher affinity than PLZF-RARa homodimers in vitro (Licht et al, 1996). PLZF-RARa/ RXRa heterodimers also bind to nonconsensus RAREs, suggesting that these heterodimers contribute to APL pathogenesis through regulation of novel gene expression (So et al, 2000). NPM-RARa and NuMA-RARa form heterodimers with RXRa; these complexes can bind and repress transcription from the RARE (Kamel-Reid et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Evidence of functional interaction between NuMA-RARα and RXRα in an in vivo model of acute promyelocytic leukemia

et al. 2008

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Acute promyelocytic leukemia (APL) is characterized by reciprocal balanced chromosomal translocations involving retinoic acid receptor-a (RARa). RARa heterodimerizes with the retinoid X receptor-a (RXRa) and transcriptionally regulates myeloid differentiation in response to ATRA (all-trans retinoic acid). Several lines of evidence suggest that APL fusion proteins interact with RXRa. To elucidate the role of RXRa in APL, we conditionally knocked out RXRa in the hCG-NuMA-RARa APL mouse model. Phenotype analysis of NuMA-RARa þ mice demonstrated that these mice developed a myeloproliferative disease-like myeloid leukemia within 4 months of birth. While hemizygous and homozygous RXRa conditional knockout mice were phenotypically normal as late as 12 months of age, we observed that the leukemic phenotype in NuMA-RARa þ mice was dependent on the presence of functional RXRa. Bone marrow promyelocyte counts were significantly reduced in NuMA-RARa þ mice with RXRa knocked down. Significant differences in the accumulations of Gr-1 þ and Mac-1 þ cells were also seen. We further observed that genes previously identified to be cooperating events in APL were also regulated in an RXRa-dependent manner. We therefore propose that the APL fusion protein NuMA-RARa cooperates with RXRa in the development of leukemia in hCG-NuMA-RARa transgenic mice and suggest a novel role for RXRa in the pathogenesis of APL.

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Retinoic acid signaling in cancer: The parable of acute promyelocytic leukemia

Ablain

2014

Intl Journal of Cancer

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Inevitably fatal some 40 years, acute promyelocytic leukemia (APL) can now be cured in more than 95% of cases. This clinical success story is tightly linked to tremendous progress in our understanding of retinoic acid (RA) signaling. The discovery of retinoic acid receptor alpha (RARA) was followed by the cloning of the chromosomal translocations driving APL, all of which involve RARA. Since then, new findings on the biology of nuclear receptors have progressively enlightened the basis for the clinical efficacy of RA in APL. Reciprocally, the disease offered a range of angles to approach the cellular and molecular mechanisms of RA action. This virtuous circle contributed to make APL one of the best-understood cancers from both clinical and biological standpoints. Yet, some important questions remain unanswered including how lessons learnt from RA-triggered APL cure can help design new therapies for other malignancies.

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The impact of differential binding of wild-type RARα, PML-, PLZF- and NPM-RARα fusion proteins towards transcriptional co-activator, RIP-140, on retinoic acid responses in acute promyelocytic leukemia

Cited by 28 publications

References 44 publications

Transcription factors and translocations in lymphoid and myeloid leukemia

Transcription factors and translocations in lymphoid and myeloid leukemia

Evidence of functional interaction between NuMA-RARα and RXRα in an in vivo model of acute promyelocytic leukemia

Retinoic acid signaling in cancer: The parable of acute promyelocytic leukemia

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