MYB and MYC in the Cell Cycle

Jm, Bishop; Eilers, Martin; Al, Katzen; Kornberg, Thomas B.; Ramsay, Gary; Schirm, Sabine

doi:10.1101/sqb.1991.056.01.014

Cited by 25 publications

(9 citation statements)

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“…No common ancestry was found when comparing these proteins; in fact, Gl1 is found on a completely distinct clade of the phylogeny away from both MIXTA and Ph1. Similar results are seen when we look at the Adapted from Takahashi (1995) and Bishop et al (1991). known members of the phenylpropanoid pathway.…”

Section: Resultssupporting

confidence: 67%

Molecular Evolution of the Myb Family of Transcription Factors: Evidence for Polyphyletic Origin

1998

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Abstract. The Myb family of proteins is a group of functionally diverse transcriptional activators found in both plants and animals that is characterized by a conserved DNA-binding domain of approximately 50 amino acids. Phylogenetic analyses of amino acid sequences of this family of proteins portray very disparate evolutionary histories in plants and animals. Animal Myb proteins have diverged from a common ancestor, while plants appear related only within the DNA-binding domain. Results imply a pattern of modular evolution of the Myb proteins centering on the possession of a helix-turn-helix motif. Based on this it is suggested that Myb proteins are a polyphyletic group related only by a ''Myb-box'' DNA-binding motif.

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Section: Resultssupporting

confidence: 67%

Molecular Evolution of the Myb Family of Transcription Factors: Evidence for Polyphyletic Origin

1998

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“…All of these results point to a strong correlation between telomere dysfunction and senescence, as well as between oxidative damage and senescence. Growth beyond the senescence checkpoint correlates with genetic lesions that interfere with one or more key cellular mortality pathways, most prominently Myc, Rb, and p53 (23,24). This is consistent with the findings that either activation of oncogenes or loss of tumor suppressor function is necessary to override the repression of telomerase in primary somatic cells.…”

supporting

confidence: 74%

Inhibition of c-Myc Oncoprotein Limits the Growth of Human Melanoma Cells by Inducing Cellular Crisis

Biroccio¹,

Amodei²,

Antonelli

et al. 2003

Journal of Biological Chemistry

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Here, we show that inhibition of c-Myc causes a proliferative arrest of M14 melanoma cells through cellular crisis, evident by the increase in size, multiple nuclei, vacuolated cytoplasm, induction of senescence-associated ␤-galactosidase activity and massive apoptosis. The c-Myc-induced crisis is associated with decreased human telomerase reverse transcriptase expression, telomerase activity, progressive telomere shortening, glutathione (GSH), depletion and, increased production of reactive oxygen species. Treatment of control cells with L-buthionine sulfoximine decreases GSH to levels of cMyc low expressing cells, but it does not modify the growth kinetic of the cells. Surprisingly, when GSH is increased in the c-Myc low expressing cells by treatment with N-acetyl-L-cysteine, cells escape crisis. To test the hypothesis that both oxidative stress and telomerase dysfunction are involved in the c-Myc-dependent crisis, we directly inhibited telomerase function and glutathione levels. Inactivation of telomerase, by expression of a catalytically inactive, dominant negative form of reverse transcriptase, reduces cellular lifespan by inducing telomere shortening. Treatment of cells with L-buthionine sulfoximine decreases GSH content and accelerates cell crisis. Analysis of telomere status demonstrated that oxidative stress affects c-Myc-induced crisis by increasing telomere dysfunction. Our results demonstrate that inhibition of c-Myc oncoprotein induces cellular crisis through cooperation between telomerase dysfunction and oxidative stress.The proliferative potential of normal cells in culture is limited to a finite number of population doublings, a phenomenon known as cellular senescence or Hayflick limit (1) that is characterized by a large, flat morphology, telomere shortening, a high frequency of nuclear abnormality and induction of ␤-galactosidase activity (2, 3). Continued cell proliferation beyond the Hayflick limit and further telomere erosion culminates in a period of massive cell death termed crisis (3). The limited capacity of human cells to replicate is an important tumorsuppressive mechanism (4), indicating that cancer cells must overcome this obstacle and achieve proliferation immortality before they can form malignant neoplasms. Direct experimental evidence implicates telomere erosion as a primary cause of cellular arrest (5, 6). Most cells with indefinite proliferative ability maintain telomeres through the expression of the catalytic subunit of the enzyme, the human telomerase reverse transcriptase (hTERT) 1 (7,8), and the introduction of telomerase into normal human cells provides telomere maintenance, prevention of senescence or crisis, and extension of life span (5, 6). In the opposite type of experiment, inhibition of telomerase in established tumor cell lines induces telomere shortening, leading to chromosome end-to-end fusions, cell death, and eventually arrest of culture growth (9 -11). Recent evidence suggests that although telomere length is an important trigger for the onset of senescence, ...

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“…Previously, we identified a single myb-related gene in the Drosophila genome (20). The Drosophila gene shares a considerably higher level of homology with vertebrate c-myb within the DNA binding domain than the other nonvertebrate genes, and unlike those genes, homology is not restricted to this domain; three additional regions of conservation are distributed throughout the protein (21). The same four regions of homology are shared with A-myb and B-myb.…”

mentioning

confidence: 98%

myb provides an essential function during Drosophila development

Katzen

Bishop

1996

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

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Vertebrate c-myb encodes a transcription factor thought to play an important role in the cell cycle. To gain further insight into myb function, we have been studying a related gene in Drosophila. We found that Drosophila myb is abundantly expressed throughout development in all mitotically active tissues, at lower levels in some postmitotic tissues, but not at detectable levels in polyploid larval tissues. We performed genetic screens to isolate recessive lethal mutations in the chromosomal region that includes the myb gene. We obtained two temperature-sensitive alleles of myb, demonstrating that the gene provides an essential function. Examination of the mutant phenotype revealed that Drosophila myb is important for both embryonic and imaginal development and that myb serves a role in the development of many tissues and during oogenesis.

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MYB and MYC in the Cell Cycle

Cited by 25 publications

References 0 publications

Molecular Evolution of the Myb Family of Transcription Factors: Evidence for Polyphyletic Origin

Molecular Evolution of the Myb Family of Transcription Factors: Evidence for Polyphyletic Origin

Inhibition of c-Myc Oncoprotein Limits the Growth of Human Melanoma Cells by Inducing Cellular Crisis

myb provides an essential function during Drosophila development

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