Expression ofmyc-family,myc-interacting, andmyc-target genes during preimplantation mouse development

Domashenko, Alevtina; Latham, Keith E.; Hatton, Kimi S.

doi:10.1002/(sici)1098-2795(199705)47:1<57::aid-mrd8>3.0.co;2-p

Cited by 36 publications

(28 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ODC expression has been detected by reverse transcription-PCR in two-cell embryos (13), and yet it is unclear whether ODC is zygotic or maternal in origin. Analysis of ODC and ␤-galactosidase expression in heterozygous embryos by immunohistochemistry at later stages of development (E10.5 to E12.5) confirmed coincident expression of the ␤-galactosidase allele and the remaining ODC wild-type allele (data not shown).…”

Section: Resultsmentioning

confidence: 99%

“…This is perhaps not surprising if one posits that maternal stores of ODC and/or polyamines are present in sufficient quantities in the embryo until E3.5. In support of this concept, ODC transcripts are detected in the oocyte by reverse transcription-PCR and continue to increase in abundance until the morula and blastocyst stages (13). In addition, DFMO treatment arrests development in vitro at the morula-to-blastocyst transition (54), whereas ODC-null embryos develop to the blastocyst stage.…”

Section: Discussionmentioning

confidence: 96%

See 1 more Smart Citation

The Ornithine Decarboxylase Gene Is Essential for Cell Survival during Early Murine Development

Pendeville

Carpino²,

Marine

et al. 2001

Molecular and Cellular Biology

229

176

View full text Add to dashboard Cite

Overexpression and inhibitor studies have suggested that the c-Myc target gene for ornithine decarboxylase (ODC), the enzyme which converts ornithine to putrescine, plays an important role in diverse biological processes, including cell growth, differentiation, transformation, and apoptosis. To explore the physiological function of ODC in mammalian development, we generated mice harboring a disrupted ODC gene. ODC-heterozygous mice were viable, normal, and fertile. Although zygotic ODC is expressed throughout the embryo prior to implantation, loss of ODC did not block normal development to the blastocyst stage. Embryonic day E3.5 ODCdeficient embryos were capable of uterine implantation and induced maternal decidualization yet failed to develop substantially thereafter. Surprisingly, analysis of ODC-deficient blastocysts suggests that loss of ODC does not affect cell growth per se but rather is required for survival of the pluripotent cells of the inner cell mass. Therefore, ODC plays an essential role in murine development, and proper homeostasis of polyamine pools appears to be required for cell survival prior to gastrulation.Overexpression of the c-Myc, N-Myc, or L-Myc members of the Myc oncogene family is a common event in human tumors. This selection likely reflects Myc's ability to provide continuous proliferative and angiogenic signals under growth-limiting conditions, such as those that occur in the tumor microenvironment (38). However, Myc's propensity to induce continuous proliferation also blocks terminal differentiation (11) and triggers the apoptotic program (2). c-Myc is a basic helix-loophelix leucine zipper protein that exhibits sequence-specific DNA binding to CACGTG or CACATG elements when dimerized with its obligate basic helix-loop-helix leucine zipper partner Max (8). Despite Myc's well-defined function as a transcriptional transactivator, the numbers of its ascribed targets that have been proven to be direct are relatively few, but they do include ornithine decarboxylase (ODC) (6), ␣-prothymosin (15), eIF-4E (44), carbamoyl-phosphate synthase-aspartate carbamoyltransferase-dihydroorotase (cad) (28), a DEAD box-related gene (MrDb) (20), the ubiquitin E2 ligase Cul1 (32), and ECA39 (7). A compelling example of a target gene that contributes to c-Myc's biological effects is ODC (34, 35), which is activated by growth factors and by c-Myc through two conserved CACGTG sites present in the first intron of vertebrate ODC genes (6). ODC is the key regulator of the polyamine biosynthetic pathway and decarboxylates L-ornithine to form putrescine (50). ODC expression is highly regulated by changes in its transcription, translation, and RNA and protein half-life (40). Furthermore, ODC enzyme activity is tightly controlled and shows biphasic induction during late G 1 and at G 2 /M (5). Inhibition of ODC by difluoromethylornithine (DFMO) compromises cell growth and transformation (3) and induces cell cycle arrest in G 1 (35,43). ODC inhibition results in marked reductions in the intracellular levels of th...

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 96%

The Ornithine Decarboxylase Gene Is Essential for Cell Survival during Early Murine Development

Pendeville

Carpino²,

Marine

et al. 2001

Molecular and Cellular Biology

229

176

View full text Add to dashboard Cite

show abstract

“…To further increase our knowledge of its significance in vivo, we have generated and characterized a Bmyc KO mouse model. Despite its high expression in early embryonic development and the lethality caused by the loss of Myc or Mycn (Nmyc) (Davis et al 1993, Domashenko et al 1997, Hurlin 2005, homozygous Bmyc KO mice were obtained. Although the KO mice proved mainly healthy and fertile, HE!HE breedings produced less homozygotes than expected by Mendelian distribution.…”

Section: Characterization Of Bmyc Knockout Micementioning

confidence: 99%

“…Lower levels of expression have been detected in several other hormonally controlled tissues, including the adrenal, pituitary, prostate, ovary, and uterus, and the protein has also been detected in the hypothalamus and testis (Gregory et al 2000). In addition, Bmyc is the predominant Myc family gene expressed during mouse preimplantation development (Domashenko et al 1997).…”

Section: Introductionmentioning

confidence: 99%

Loss of Bmyc results in increased apoptosis associated with upregulation of Myc expression in juvenile murine testis

Turunen

Sipilä²,

Strauss³

et al. 2012

Reproduction

View full text Add to dashboard Cite

Bmyc is a member of the Myc family of transcriptional regulators in the mouse and the rat. It is predominantly expressed in hormonally controlled tissues, with highest level of expression in the epididymis. The BMYC protein has been shown to function as a transcription factor in vitro and to inhibit MYC. To study the significance of BMYC in vivo, a Bmyc knockout (KO) mouse model was generated by homologous recombination. The KO mice were viable and fertile and did not display gross morphological or histological changes compared to the WT mice. However, the testes and the epididymides of the KO mice were smaller than those of the WT mice. Correspondingly, a tendency for a lower sperm concentration in the cauda epididymides of the KO mice was detected. The testosterone produced/testis was significantly reduced, and accordingly, the LH levels were increased in the KO mice. Also, the expression levels of Myc and several of its target genes were elevated in the testes of prepubertal KO mice, whereas no differences in gene expression levels were detected in adult mice. Associated with the increased Myc expression, more apoptotic spermatogenic cells were detected in the seminiferous tubules of the KO mice. In conclusion, our data suggest that Bmyc is a regulator of Myc in vivo and that overexpression of Myc in the developing testis leads to increased apoptosis of spermatogenic cells.

show abstract

“…A possible role for B-Myc in di erentiation is indicated by the observation that Bmyc expression was much lower in the undi erentiated pituitary cell line, aT3-1 compared to the more di erentiated pituitary lines, LbT2 and GH3. Also, B-myc mRNA is strongly induced when the trophectoderm lineage, the ®rst embryonic cell lineage to undergo di erentiation, is beginning to di erentiate (Domashenko et al, 1997) suggesting a role in very early di erentiative events. B-Myc most likely does not have a general role in di erentiation or proliferation, since B-myc expression was not regulated upon induction of di erentiation or by serum starvation of the F9 embryonal carcinoma cell line (Ingvarsson et al, 1988b).…”

Section: Expression Of B-myc In Hormonally-regulated Tissuesmentioning

confidence: 99%

B-Myc is preferentially expressed in hormonally-controlled tissues and inhibits cellular proliferation

2000

View full text Add to dashboard Cite

The myc family of genes plays an important role in several cellular processes including proliferation, apoptosis, di erentiation, and transformation. B-myc, a relatively new and largely unstudied member of the myc family, encodes a protein that is highly homologous to the N-terminal transcriptional regulatory domain of cMyc. Here, we show that high level B-myc expression is restricted to speci®c mouse tissues, primarily hormonally-controlled tissues, with the highest level of expression in the epididymis. We also report the identi®cation of the endogenous B-Myc protein from mouse tissues. Like other Myc family proteins, B-Myc is a short-lived nuclear protein which is phosphorylated on residues Ser-60 and Ser-68. Rapid proteolysis of B-Myc occurs via the ubiquitin-proteasome pathway. Finally, we found that overexpression of B-Myc signi®cantly slows the growth of Rat 1a ®broblasts and COS cells suggesting B-Myc functions as an inhibitor of cellular proliferation.

show abstract

Expression ofmyc-family,myc-interacting, andmyc-target genes during preimplantation mouse development

Cited by 36 publications

References 64 publications

The Ornithine Decarboxylase Gene Is Essential for Cell Survival during Early Murine Development

The Ornithine Decarboxylase Gene Is Essential for Cell Survival during Early Murine Development

Loss of Bmyc results in increased apoptosis associated with upregulation of Myc expression in juvenile murine testis

B-Myc is preferentially expressed in hormonally-controlled tissues and inhibits cellular proliferation

Contact Info

Product

Resources

About