Critical Residues within the BTB Domain of PLZF and Bcl-6 Modulate Interaction with Corepressors

Melnick, Ari; Carlile, Graeme W.; Ahmad, Kami; Kiang, C.L.; Corcoran, Connie M.; Bardwell, Vivian J.; Privé, G.G.; Licht, Jonathan D.

doi:10.1128/mcb.22.6.1804-1818.2002

Cited by 199 publications

(211 citation statements)

References 55 publications

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“…PLZF recruits histone deacetylase complexes via its C-terminal zinc fingers to repress transcription (30,31). Here we show that RARα-PLZF interacts with HDAC1 in vitro (Fig.…”

Section: Rarα-plzf Decreases the Expression Of C/ebpα Target Genes Wimentioning

confidence: 81%

RARα-PLZF oncogene inhibits C/EBPα function in myeloid cells

Girard

Tremblay

Humbert

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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In acute promyelocytic leukemia, granulocytic differentiation is arrested at the promyelocyte stage. The variant t(11;17) translocation produces two fusion proteins, promyelocytic leukemia zinc finger-retinoic acid receptor α (PLZF-RARα) and RARα-PLZF, both of which participate in leukemia development. Here we provide evidence that the activity of CCAAT/enhancer binding protein α (C/EBPα), a master regulator of granulocytic differentiation, is severely impaired in leukemic promyelocytes with the t(11;17) translocation compared with those associated with the t(15;17) translocation. We show that RARα-PLZF inhibits myeloid cell differentiation through interactions with C/EBPα tethered to DNA, using ChIP and DNA capture assays. Furthermore, RARα-PLZF recruits HDAC1 and causes histone H3 deacetylation at C/EBPα target loci, thereby decreasing the expression of C/EBPα target genes. In line with these results, HDAC inhibitors restore in part C/EBPα target gene expression. These findings provide molecular evidence for a mechanism through which RARα-PLZF acts as a modifier oncogene that subverts differentiation in the granulocytic lineage by associating with C/EBPα and inhibiting its activity.APL | granulocyte differentiation | transcription inhibition | histone modification | protein interaction

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“…PLZF recruits histone deacetylase complexes via its C-terminal zinc fingers to repress transcription (30,31). Here we show that RARα-PLZF interacts with HDAC1 in vitro (Fig.…”

Section: Rarα-plzf Decreases the Expression Of C/ebpα Target Genes Wimentioning

confidence: 81%

RARα-PLZF oncogene inhibits C/EBPα function in myeloid cells

Girard

Tremblay

Humbert

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…32). This domain mediates transcriptional repression through its ability to recruit the corepressors SMRT and N-CoR, as demonstrated for BCL-6 and PLZF (33)(34)(35). The Bach1 BTB domain mediates oligomer formation, generating a multivalent DNA-binding complex (25,32).…”

Section: Bach1 Export From Nuclei Is Dependent On Crm1/exportin-1-mentioning

confidence: 99%

Cadmium Induces Nuclear Export of Bach1, a Transcriptional Repressor of Heme Oxygenase-1 Gene

Sano

Tashiro

Sun

et al. 2003

Journal of Biological Chemistry

156

128

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The export of certain nuclear proteins is involved in the regulation of various nuclear functions, including transcription. In some cases, the export of target proteins is induced upon environmental or cellular cues, resulting in conditional gene expression. The small Maf proteins appear to be critical regulators of heme oxygenase (HO)-1, an anti-oxidant defense enzyme that degrades heme into iron, carbon monoxide, and biliverdin. Although ho-1 is repressed by Bach1/small Maf heterodimers, it is activated by Nrf2/small Maf heterodimers, indicating that Bach1 and Nrf2 compete with each other. We anticipated that the nuclear concentration of Bach1 might be regulated to ensure that the entire system effectively responds to various stimuli. We carried out detailed domain analysis of Bach1 in an effort to understand how various inducers of HO-1 inactivate Bach1. We show here that cadmium, a strong inducer of HO-1, activates the nuclear export of Bach1. This cadmium-induced export of Bach1 was mediated in trans by its C-terminal region that is conserved between Bach1 and Bach2. The nuclear export of Bach2 was also induced by cadmium, indicating that the cadmium responsibility is shared between Bach1 and Bach2. The nuclear export of Bach1 was dependent on Crm1/Exportin-1 as well as the extracellular signal-regulated kinase-1/2 (ERK1/2) activity. These results indicate that the nuclear export of Bach1 constitutes an important regulatory mechanism to relieve the Bach1-mediated repression of genes such as ho-1.

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“…The BTB/POZ domain of PLZF is an evolutionarily conserved protein-protein interaction domain found in essential transcriptional regulators involved in a variety of important developmental processes, such as in homeostasis, neoplasia, apoptosis, cell growth, proliferation, differentiation, nuclear sub-localization, and transcriptional repression during pattern formation in embryogenesis [14][15][16][17][18][19][20][21]. The BTB/POZ domain is also strongly implicated in the regulation of gene expression through the local chromatin conformation.…”

Section: Introductionmentioning

confidence: 99%

A novel cervical cancer suppressor 3 (CCS‐3) interacts with the BTB domain of PLZF and inhibits the cell growth by inducing apoptosis

Rho

Park

et al. 2006

FEBS Letters

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Promyelocytic leukemia zinc finger protein (PLZF) is a sequence-specific, DNA binding, transcriptional repressor differentially expressed during embryogenesis and in adult tissues. PLZF is known to be a negative regulator of cell cycle progression. We used PLZF as bait in a yeast two-hybrid screen with a cDNA library from the human ovary tissue. A novel cervical cancer suppressor 3 (CCS-3) was identified as a PLZF interacting partner. Further characterization revealed the BTB domain as an interacting domain of PLZF. Interaction of CCS-3 with PLZF in mammalian cells was also confirmed by co-immunoprecipitation and in vitro binding assays. It was found that, although CCS-3 shares similar homology with eEF1A, the study determined CCS-3 to be an isoform. CCS-3 was observed to be downregulated in human cervical cell lines as well as in cervical tumors when compared to those from normal tissues. Overexpression of CCS-3 in human cervical cell lines inhibits cell growth by inducing apoptosis and suppressing human cyclin A2 promoter activity. These combined results suggest that the potential tumor suppressor activity of CCS-3 may be mediated by its interaction with PLZF.

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Critical Residues within the BTB Domain of PLZF and Bcl-6 Modulate Interaction with Corepressors

Cited by 199 publications

References 55 publications

RARα-PLZF oncogene inhibits C/EBPα function in myeloid cells

RARα-PLZF oncogene inhibits C/EBPα function in myeloid cells

Cadmium Induces Nuclear Export of Bach1, a Transcriptional Repressor of Heme Oxygenase-1 Gene

A novel cervical cancer suppressor 3 (CCS‐3) interacts with the BTB domain of PLZF and inhibits the cell growth by inducing apoptosis

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