E2F-1 Functions in Mice to Promote Apoptosis and Suppress Proliferation

Field, Seth J.; Tsai, Fong-Ying; Kuo, Frank C.; Zubiaga, Ana M.; Kaelin, William G.; Livingston, David M.; Orkin, Stuart H.; Greenberg, Michael E.

doi:10.1016/s0092-8674(00)81255-6

Cited by 715 publications

(596 citation statements)

References 61 publications

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“…We assessed the contribution of the genetic background to the phenotype by breeding the animals to C57Bl/6J‐strain, which showed that genetic background had a strong influence on the severity and the time course of the phenotype associated with E2F1 loss. In the previous studies on the E2F1 −/− mice the testicular atrophy has been reported from the age of 3 months onwards (Field et al ., 1996; Yamasaki et al ., 1996; Hoja et al ., 2004). In contrast, in C57Bl/6 genetic background significant testicular atrophy occurred already at P20.…”

Section: Discussionmentioning

confidence: 99%

“…All procedures were carried out according to the institutional and ethical policies of the University of Turku and approved by the local ethics committee on animal experimentation. The E2f‐1 −/− mice B6;129S4‐E2f1tm1Meg/J (Field et al ., 1996; Yamasaki et al ., 1996) were purchased from the Jackson Laboratory. C57BI/6J control animals were obtained from the breeding stocks of the Central Animal Laboratory of the University of Turku.…”

Section: Methodsmentioning

confidence: 99%

“…Both loss and overexpression of E2f1 led to disruption of spermatogenesis in the mouse (Yamasaki et al ., 1996; Agger et al ., 2005). In the first reports on the E2f1 knockout phenotype, testicular atrophy was observed from the age of 3 months onwards (Field et al ., 1996; Yamasaki et al ., 1996). When transgenic overexpression of E2f1 was induced in the adult testis, a rapid increase in apoptosis of spermatocytes was observed and a long exposure to the transgene resulted in accumulation of GCNIS‐like cells and loss of more mature germ cells (Agger et al ., 2005).…”

Section: Introductionmentioning

confidence: 99%

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E2F1 controls germ cell apoptosis during the first wave of spermatogenesis

et al. 2015

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SummaryCell cycle control during spermatogenesis is a highly complex process owing to the control of the mitotic expansion of the spermatogonial cell population and following meiosis, induction of DNA breaks during meiosis and the high levels of physiological germ‐cell apoptosis. We set out to study how E2F1, a key controller of cell cycle, apoptosis, and DNA damage responses, functions in the developing and adult testis. We first analyzed the expression pattern of E2f1 during post‐natal testis development using RNA in situ hybridization, which showed a differential expression pattern of E2f1 in the adult and juvenile mouse testes. To study the function of E2f1, we took advantage of the E2F1−/− mouse line, which was back‐crossed to C57Bl/6J genetic background. E2f1 loss led to a severe progressive testicular atrophy beginning at the age of 20 days. Spermatogonial apoptosis during the first wave of spermatogenesis was decreased. However, already in the first wave of spermatogenesis an extensive apoptosis of spermatocytes was observed. In the adult E2F1−/− testes, the atrophy due to loss of spermatocytes was further exacerbated by loss of spermatogonial stem cells. Surprisingly, only subtle changes in global gene expression array profiling were observed in E2F1−/− testis at PND20. To dissect the changes in each testicular cell type, an additional comparative analysis of the array data was performed making use of previously published data on transcriptomes of the individual testicular cell types. Taken together, our data indicate that E2F1 has a differential role during first wave of spermatogenesis and in the adult testis, which emphasizes the complex nature of cell cycle control in the developing testis.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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E2F1 controls germ cell apoptosis during the first wave of spermatogenesis

et al. 2015

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“…Many genes involved in apoptosis are direct targets of E2F, overexpression of E2F 1 has been shown to induce apoptosis, and E2F 1À/À thymocytes are defective in undergoing apoptosis (Field et al, 1996). Whether this ability to induce apoptosis is restricted to E2F 1 or is shared by other activating E2Fs is still unclear.…”

Section: Cell Cycle Roles Of the Rb Family Of Proteinsmentioning

confidence: 99%

Retinoblastoma family genes

2006

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“…Recent evidence suggests that it is likely that di erent members of the E2F family may perform distinct functions in an organism. First, mice nullizygous for the E2F-1 gene display a strong predisposition to hyperplastic growth and tumor formation (Field et al, 1996;Yamasaki et al, 1996). These results suggest that other members of the E2F family cannot compensate for the functional loss of E2F-1.…”

Section: Introductionmentioning

confidence: 99%

E2F-3 accumulation is regulated by polypeptide stability

1998

Oncogene

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E2F is a complex family of transcription factors which appears to regulate the transcription of genes required for the S phase of the mammalian cell cycle. In the present work, we have examined the mechanisms regulating E2F-3 accumulation in mouse ®broblasts. We have determined that E2F-3 DNA binding activity is restricted to the G 1 /S transition and S phase in both normal BALB/c-3T3 ®broblasts and in an SV40 virustransformed BALB/c-3T3 derivative. Immunoblot analysis indicates that G 0 and G 1 cells have little or no E2F-3 polypeptide and that the increase in the DNA binding activity of E2F-3 at the G 1 /S boundary is re¯ected by an increase in total E2F-3 protein. In contrast to the E2F-3 polypeptide, RNAse protection assays demonstrate that the E2F-3 mRNA is clearly present in G 0 and G 1 cells. Finally, pulse/chase experiments indicate that the halflife of E2F-3 is approximately 40-fold greater in cells blocked in S phase relative to asynchronously growing cells. Together, these results indicate that the accumulation E2F-3 at S phase may be regulated, at least in part, at the level of protein stability.

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E2F-1 Functions in Mice to Promote Apoptosis and Suppress Proliferation

Cited by 715 publications

References 61 publications

E2F1 controls germ cell apoptosis during the first wave of spermatogenesis

E2F1 controls germ cell apoptosis during the first wave of spermatogenesis

Retinoblastoma family genes

E2F-3 accumulation is regulated by polypeptide stability

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