c-Myb associates with PML in nuclear bodies in hematopoietic cells

Dahle, Øyvind; Bakke, Oddmund; Gabrielsen, Odd S.

doi:10.1016/j.yexcr.2004.03.014

Cited by 19 publications

(15 citation statements)

References 43 publications

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“…While this remains to be tested, there are published studies that appear to support this possibility. For example, ATBF1 could cooperate with PML NBs to regulate activities of the Myb oncoprotein, because Myb is subjected to SUMOylation for activity regulation, it localizes to PML NBs via direct interaction with PML, and it also directly interacts with ATBF1 to regulate its activity [42], [46]. As a large protein that associates with PML NBs, ATBF1 could be part of the PML NB scaffold for protein SUMOylation to occur.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Nuclear Localization and SUMOylation of the ATBF1 Transcription Factor in Epithelial Cells

Sun

Dong

et al. 2014

PLoS ONE

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ATBF1/ZFHX3 is a large transcription factor that functions in development, tumorigenesis and other biological processes. ATBF1 is normally localized in the nucleus, but is often mislocalized in the cytoplasm in cancer cells. The mechanism underlying the mislocalization of ATBF1 is unknown. In this study, we analyzed the nuclear localization of ATBF1, and found that ectopically expressed ATBF1 formed nuclear body (NB)-like dots in the nucleus, some of which indeed physically associated with promyelocytic leukemia (PML) NBs. We also defined a 3-amino acid motif, KRK2615-2617, as the nuclear localization signal (NLS) for ATBF1. Interestingly, diffusely distributed nuclear SUMO1 proteins were sequestered into ATBF1 dots, which could be related to ATBF1's physical association with PML NBs, known SUMOylation hotspots. Furthermore, ATBF1 itself was SUMOylated. ATBF1 SUMOylation occurred at more than 3 lysine residues including K2349, K2806 and K3258 and was nuclear specific. Finally, the PIAS3 SUMO1 E3 ligase, which interacts with ATBF1 directly, diminished rather than enhanced ATBF1 SUMOylation, preventing the co-localization of ATBF1 with SUMO1 in the nucleus. These findings suggest that nuclear localization and SUMOylation are important for the transcription factor function of ATBF1, and that ATBF1 could cooperate with PML NBs to regulate protein SUMOylation in different biological processes.

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Section: Discussionmentioning

confidence: 99%

Characterization of Nuclear Localization and SUMOylation of the ATBF1 Transcription Factor in Epithelial Cells

Sun

Dong

et al. 2014

PLoS ONE

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“…As seen in Figure 5a, the FLASH and spliceosome nuclear foci are clearly not co-localized. We have earlier reported that c-Myb co-localizes with PML nuclear bodies (Dahle et al, 2004). We therefore addressed the association between FLASH and PML.…”

Section: Flash Interacts With the Dna-binding Domain Of C-mybmentioning

confidence: 98%

FLASH acts as a co-activator of the transcription factor c-Myb and localizes to active RNA polymerase II foci

et al. 2008

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The c-Myb oncoprotein is a DNA-binding transcription factor with a key role in early stages of hematopoiesis. To expand our knowledge of partners cooperating with c-Myb, we performed a yeast two-hybrid screening with full-length c-Myb as bait. Here, we report FLICEassociated huge protein (FLASH)/CASP8AP2 as a novel Myb-interacting protein. We show that FLASH interacts with the DNA-binding domain of c-Myb and enhances c-Myb-dependent reporter activity and expression of endogenous c-Myb target genes. Chromatin immunoprecipitation assays revealed that FLASH and c-Myb both associate with the MYC promoter region as well as with the intronic enhancer of the c-Myb target gene ADA. Furthermore, siRNA knock-down of FLASH or c-Myb both result in a reduction of MYC and ADA expression. The co-activator effect is mediated through the C-terminal part of FLASH, which binds c-Myb. The FLASH-induced enhancement is comparable with the increase seen with the c-Myb co-activator p300. We find FLASH localized in discrete nuclear speckles in several cell lines, co-localized with c-Myb in active RNA polymerase II foci. These results imply a novel molecular mechanism of regulation of c-Myb activity. We propose that c-Myb cooperates with FLASH in foci associated with active RNA polymerase II, leading to enhancement of Myb-dependent gene activation.

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“…28 Confocal fluorescent images were collected with a Bio-Rad (Hercules, CA) MRC 1024 confocal scan head mounted on a Nikon Optiphot microscope with a 60 ϫ planapochromat lens in the Confocal Core Facility, Center for Cancer Research, NCI. A krypton-argon gas laser provided excitation at 488 nm.…”

Section: Western Blot and Immunofluorescence Analysismentioning

confidence: 99%

PML mediates IFN-α–induced apoptosis in myeloma by regulating TRAIL induction

Crowder

Dahle

Davis

et al. 2005

Blood

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Interferon (IFN) induces expression of proapoptotic genes and has been used in the clinical treatment of multiple myeloma. The promyelocytic leukemia (PML) gene is an IFN-induced target that encodes a tumor suppressor protein. PML protein is typically localized within discrete speckled nuclear structures termed PML nuclear bodies (NBs). Multiple myeloma cells demonstrate differential responses to IFN treatment, the mechanism of which is largely unknown. Herein, we show that growth inhibition effects of IFN-alpha in myeloma cells correlate with PML NBs and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induction, whereas known IFN targets including signal transducer and activator of transcription-1 (STAT1), STAT3, p38, and Daxx cannot account for these differential responses. RNAi silencing of PML blocks IFN-alpha-induced apoptosis in myeloma cells and correspondingly down-regulates TRAIL expression. Similarly, stable expression of a dominant negative TRAIL receptor DR5 partially blocks IFN-induced cell death. These results demonstrate that PML and TRAIL play important roles in IFN-induced apoptosis and identify TRAIL as a novel downstream transcriptional target of PML. Identification of PML and PML NBs as effectors of IFN responses provides insights into mechanisms by which tumor cells exhibit resistance to this class of agents and may prove useful in assessing treatment regimens.

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c-Myb associates with PML in nuclear bodies in hematopoietic cells

Cited by 19 publications

References 43 publications

Characterization of Nuclear Localization and SUMOylation of the ATBF1 Transcription Factor in Epithelial Cells

Characterization of Nuclear Localization and SUMOylation of the ATBF1 Transcription Factor in Epithelial Cells

FLASH acts as a co-activator of the transcription factor c-Myb and localizes to active RNA polymerase II foci

PML mediates IFN-α–induced apoptosis in myeloma by regulating TRAIL induction

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