Expression cloning of a cDNA encoding a retinoblastoma-binding protein with E2F-like properties

Kaelin, William G.; Krek, Wilhelm; Sellers, William R.; DeCaprio, James A.; Ajchenbaum, Florence; Fuchs, Charles S.; Chittenden, Thomas; Li, Yue; Farnham, Peggy J.; Blanar, Michael A.; Livingston, David M.; Flemington, Erik K.

doi:10.1016/0092-8674(92)90108-o

Cited by 832 publications

(757 citation statements)

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“…Several other cellular proteins which have been shown to stably interact with cyclin/cdk complexes also contain a region that is homologous to the p130 cyclin binding region. Included among these are the highly related p107 protein, the cdk inhibitors p21 cip1 , p27 kip1 , p57 kip2 (ElDeiry et al, 1993;Gu et al, 1993;Harper et al, 1993;Xiong et al, 1993;Polyak et al, 1994;Toyoshima and Hunter, 1994;Lee et al, 1995;Matsuoka et al, 1995) and the transcription factor E2F-1 (Helin et al, 1992;Kaelin et al, 1992;Shan et al, 1992). A similar sequence is found in E2F-2 and -3; however, these proteins have not been demonstrated to interact with the cyclin/cdk complexes (Ivey-Hoyle et al, 1993;Lees et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

“…An examination of the sequences of various other cyclin/cdk interacting proteins revealed sequences similar to the p130 RRRLFVE motif in several other proteins including E2F-1, 2 and 3, p21 cip1 , p27 kip1 and p57 kip2 (Helin et al, 1992;Kaelin et al, 1992;Shan et al, 1992;El-Deiry et al, 1993;Gu et al, 1993;Harper et al, 1993;Ivey-Hoyle et al, 1993;Lees et al, 1993;Xiong et al, 1993;Polyak et al, 1994;Toyoshima and Hunter, 1994;Lee et al, 1995;Matsuoka et al, 1995) (Figure 5a). As discussed below, each of these proteins has been shown to be present in complexes containing cyclin A or E. In some cases, this particular region has been implicated in the cyclin interactions.…”

Section: P130 Amino Acids Interacting With Cyclins Are Conserved In Omentioning

confidence: 96%

“…Particularly noteworthy among these are the interactions with the E2F/DP family of transcription factors (Cao et al, 1992;Devoto et al, 1992;Helin et al, 1992Helin et al, , 1993Kaelin et al, 1992;Shan et al, 1992;Shirodkar et al, 1992;Cobrinik et al, 1993;Ivey-Hoyle et al, 1993;Lees et al, 1993;Bandara et al, 1994;Bejersbergen et al, 1994;Ginsberg et al, 1994;Buck et al, 1995;Hijmans et al, 1995;Ormondroyd et al, 1995;Sardet et al, 1995;Wu et al, 1995;Zhang and Chellappan, 1995). The E2F transcription factors are thought to control expression of a number of genes involved in cell cycle progression (reviewed in Cobrinik, 1996).…”

Section: Introductionmentioning

confidence: 99%

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Identification of a p130 domain mediating interactions with cyclin A/cdk 2 and cyclin E/cdk 2 complexes

Lacy

Whyte

1997

Oncogene

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Section: Discussionmentioning

confidence: 99%

Section: P130 Amino Acids Interacting With Cyclins Are Conserved In Omentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Identification of a p130 domain mediating interactions with cyclin A/cdk 2 and cyclin E/cdk 2 complexes

Lacy

Whyte

1997

Oncogene

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“…E2F1 is a member of the eight‐member E2F‐protein‐family that controls cell cycle, apoptosis, DNA damage response, and cell differentiation (for review see (Chen et al ., 2009)). Since its discovery, E2F1 has been implicated as a direct target of the retinoblastoma tumor suppressor protein (Helin et al ., 1992; Kaelin et al ., 1992; Shan et al ., 1992). In quiescent cells hypophosphorylated RB binds E2F1 and inhibits E2F‐mediated transcription.…”

Section: Introductionmentioning

confidence: 99%

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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“…Members of the Rb family have been shown to possess a strong transcriptional repression activity when tethered to a promoter (Adnane et al, 1995;Sellers et al, 1995;Weintraub et al, 1992Weintraub et al, , 1995, and thus, cell cyclespeci®c repression conferred by an E2F site is likely mediated by trimeric E2F complexes which contain one member of the Rb family. Cell cycle-speci®c activation by E2F is likely mediated by dimeric E2F which possesses a potent transcriptional activation domain (Helin et al, 1992;Kaelin et al, 1992;Shan et al, 1992), as well as the ability to bend DNA (Cress and Nevins, 1996), both of which may contribute to promoter activation. Cellular E2F activity is formed by heterodimers of one member of the E2F family and one member of the DP family or heterotrimers which also include one member of the Rb family (for a review see reference Slansky and Farnham, 1996).…”

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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Expression cloning of a cDNA encoding a retinoblastoma-binding protein with E2F-like properties

Cited by 832 publications

References 59 publications

Identification of a p130 domain mediating interactions with cyclin A/cdk 2 and cyclin E/cdk 2 complexes

Identification of a p130 domain mediating interactions with cyclin A/cdk 2 and cyclin E/cdk 2 complexes

E2F1 controls germ cell apoptosis during the first wave of spermatogenesis

E2F-3 accumulation is regulated by polypeptide stability

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