MYB function in normal and cancer cells

Ramsay, Robert G.; Gonda, Thomas J.

doi:10.1038/nrc2439

Cited by 545 publications

(607 citation statements)

References 142 publications

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“…The importance of MYB and GATA1 in the normal hematopoietic tissue as well as for the onset of hematological malignancies has been extensively studied. 3,4 Deregulation of MYB expression has been suggested as a relevant occurence in the proliferation of human malignancies, possibly affecting over 80 MYB target genes. Specific genomic abnormalities have been reported in T-cell acute lymphoblastic leukemia, 3 resulting in either a cryptic duplication within the MYB locus or a t(6;7)(q23;q34) rearrangement, juxtaposing TCRB and MYB in a new chimeric product.…”

Section: As Indicated Inmentioning

confidence: 99%

“…High levels of MYB and low levels of GATA1 characterize the early stages of hematopoiesis: as differentiation progresses, an inverse regulation takes place ultimately leading to high levels of GATA1 and low levels of MYB in terminally differentiated cells. 3 The role of MYB and GATA1 has been explored through various in vivo studies. Several animal models that expressed reduced levels of GATA1 were used to study the effects of its deficiency.…”

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confidence: 99%

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In vivo expression of an aberrant MYB-GATA1 fusion induces leukemia in the presence of GATA1 reduced levels

et al. 2011

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Section: As Indicated Inmentioning

confidence: 99%

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confidence: 99%

In vivo expression of an aberrant MYB-GATA1 fusion induces leukemia in the presence of GATA1 reduced levels

et al. 2011

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“…Such a feedback mechanism might be important to control the proliferation-stimulating activity of c-Myb and would be consistent with Pdcd4's function as a tumor suppressor. This might be relevant, for example, in colon cancer in which downregulation of Pdcd4 expression and increased c-myb expression are frequently associated with highly malignant states (Mudduluru et al, 2007;Ramsay and Gonda, 2008). The identification of c-myb mRNA as a target of Pdcd4 has allowed, for the first time, to examine how Pdcd4 is targeted to a specific mRNA.…”

Section: Discussionmentioning

confidence: 99%

Pdcd4 directly binds the coding region of c-myb mRNA and suppresses its translation

et al. 2011

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Pdcd4 is a novel tumor suppressor protein that functions in the nucleus and the cytoplasm, and appears to be involved in the regulation of transcription and translation. In the cytoplasm, Pdcd4 has been implicated in the suppression of translation of mRNAs containing structured 5 0 -untranslated regions; however, the mechanisms that recruit Pdcd4 to specific target mRNAs and the identities of these mRNAs are mostly unknown. In this study, we have identified c-myb mRNA as the first natural translational target mRNA of Pdcd4. We have found that translational suppression of c-myb mRNA by Pdcd4 is dependent on sequences located within the c-myb-coding region. Furthermore, we have found that the N-terminal domain of Pdcd4 has an important role in targeting Pdcd4 to c-myb RNA by mediating preferential RNA binding to the Pdcd4-responsive region of c-myb mRNA. Overall, our work demonstrates for the first time that Pdcd4 is directly involved in translational suppression of a natural mRNA and provides the first evidence for a key role of the RNA-binding domain in targeting Pdcd4 to a specific mRNA.

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“…Myb overexpression is a feature of colorectal cancer (20) and here we demonstrate that Myb is a transactivator of Ccne1. We observe coexpression of Myb and Cyclin E1 protein within intestinal cells and adenomas and show that Cyclin E1 expression is coupled to Myb function in adenomas and intestinal organoids.…”

Section: Introductionmentioning

confidence: 88%

Defective Myb Function Ablates Cyclin E1 Expression and Perturbs Intestinal Carcinogenesis

Cheasley

Pereira

Sampurno

et al. 2015

Molecular Cancer Research

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Cyclin E1 is essential for the reentry of quiescent cells into the cell cycle. When hypomorphic mutant Myb mice (Myb Plt4 ) were examined, it was noted that Cyclin E1 (Ccne1) expression was reduced. Furthermore, the induction of Ccne1 in recovering intestinal epithelia following radiation-induced damage was ablated in Myb-mutant mice. These data prompted us to investigate whether Myb directly regulated Ccne1 and to examine whether elevated Myb in colorectal cancer is responsible for Cyclin E1-driven tumor growth. Here, it was found that Myb/ MYB and Ccne1/CCNE1 expressions were coupled in both mouse and human adenomas. In addition, the low molecular weight Cyclin E1 was the predominant form in intestinal crypts and adenomatous polyposis coli (Apc)-mutant adenomas. Chromatin immunoprecipitation (ChIP) analysis confirmed that Myb bound directly to the Ccne1 promoter and regulated its endogenous expression. In contrast, Myb Plt4 served as a dominant-negative factor that inhibited wild-type Myb and this was not apparently compensated for by the transcription factor E2F1 in intestinal epithelial cells. Myb Plt4/Plt4 mice died prematurely on an Apc Min/þ background associated with hematopoietic defects, including a myelodysplasia; nevertheless, Apc Min/þ mice were protected from intestinal tumorigenesis when crossed to Myb Plt4/þ mice. Knockdown of CCNE1 transcript in murine colorectal cancer cells stabilized chromosome ploidy and decreased tumor formation. These data suggest that Cyclin E1 expression is Myb dependent in normal and transformed intestinal epithelial cells, consistent with a cell-cycle progression and chromosome instability role in cancer.Implications: This study demonstrates that Myb regulates Cyclin E1 expression in normal gastrointestinal tract epithelial cells and is required during intestinal tumorigenesis. Mol Cancer Res; 13(8); 1185-96. Ó2015 AACR.

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MYB function in normal and cancer cells

Cited by 545 publications

References 142 publications

In vivo expression of an aberrant MYB-GATA1 fusion induces leukemia in the presence of GATA1 reduced levels

In vivo expression of an aberrant MYB-GATA1 fusion induces leukemia in the presence of GATA1 reduced levels

Pdcd4 directly binds the coding region of c-myb mRNA and suppresses its translation

Defective Myb Function Ablates Cyclin E1 Expression and Perturbs Intestinal Carcinogenesis

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