Cell cycle in mouse development

Ciemerych, Maria A.; Sicinski, Peter

doi:10.1038/sj.onc.1208608

Cited by 146 publications

(112 citation statements)

References 279 publications

(318 reference statements)

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“…The retinoblastoma protein (pRB) was the first member described and it became readily clear that its inactivation via phosphorylation first by cyclin D/cyclin-dependent kinase (CDK)4,6 in mid-G 1 and then by cyclin E/CDK2 in late G 1 was critical to pass the restriction point and commit cells to replicate their DNA and divide (reviewed in Ciemerych and Sicinski, 2005). The initial inactivation by CDK4 results in derepression of the cyclin E gene, and the consequent increase in cyclin E protein leads to the activation of CDK2, which further inactivates pRB having as a final outcome the transcription of S phase genes (recently reviewed in Sherr and Roberts, 2004;Ciemerych and Sicinski, 2005). However, the discovery of remaining members of the family, p107 and p130, revealed that G 1 -S progression had additional layers of complexity (recently reviewed in Classon and Dyson, 2001;Classon and Harlow, 2002;Du and Pogoriler, 2006).…”

Section: Introductionmentioning

confidence: 99%

Mammalian Mip/LIN-9 interacts with either the p107, p130/E2F4 repressor complex or B-Myb in a cell cycle-phase-dependent context distinct from the Drosophila dREAM complex

2007

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Mammalian Mip/LIN-9 is a cell cycle regulatory protein that is negatively regulated by CDK4/cyclin D. It has been demonstrated that Mip/LIN-9 collaborates with B-Myb during S and G 2 /M in the induction of cyclins A and B, and CDK1. The ortholog of Mip/LIN-9 in Drosophila, Mip130, is part of a large multisubunit protein complex that includes RBF, repressor E2Fs and Myb, in what was termed the dREAM complex. A similar complex, although lacking B-Myb, was also described in Caenorhabditis elegans. Here, we demonstrate that unlike Drosophila, Mip/LIN-9 has mutually exclusive and cell cycle-phasespecific interactions with the mammalian orthologs of the dREAM complex. In G 0 /early G 1 , Mip/LIN-9 forms a complex with E2F4 and p107 or p130, while in late G 1 /S phase, it associates with B-Myb. The separation of Mip/LIN-9 from p107,p130/E2F4 is likely driven by phosphorylation of the pocket proteins by CDK4 since Mip/LIN-9 fails to interact with phosphorylated forms of p107,p130. Importantly, the repressor complex that Mip/LIN-9 forms with p107 takes functional precedence over the transcriptional activation linked to the Mip/LIN-9 and B-Myb interaction since expression of p107 blocks the activation of the cyclin B promoter triggered by B-Myb and Mip/LIN-9.

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Section: Introductionmentioning

confidence: 99%

Mammalian Mip/LIN-9 interacts with either the p107, p130/E2F4 repressor complex or B-Myb in a cell cycle-phase-dependent context distinct from the Drosophila dREAM complex

2007

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“…In normal cells, Cyclin E/CDK2 activity is associated with DNA replication-related functions. [15][16][17] Ectopic expression of Cyclin E accelerates G1 progression, while inhibition of Cyclin E/CDK2 activity prevents S phase entry, indicating a positive role for this complex in G1/S transition. [18][19] Overexpression of Cyclin E interferes with pre-replication complex assembly, causing replication stress and genomic instability.…”

Section: Introductionmentioning

confidence: 99%

“…14 Cell cycle progression is precisely controlled by the activation of specific cyclin-dependent kinases (CDKs) and their partner cyclins. [15][16] Cyclin E normally accumulates at the G1/S phase transition, where it promotes S phase entry and progression by binding to and activating CDK2. In normal cells, Cyclin E/CDK2 activity is associated with DNA replication-related functions.…”

Section: Introductionmentioning

confidence: 99%

NFAT1 transcription factor regulates cell cycle progression and cyclin E expression in B lymphocytes

et al. 2016

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The NFAT family of transcription factors has been primarily related to T cell development, activation, and differentiation. Further studies have shown that these ubiquitous proteins are observed in many cell types inside and outside the immune system, and are involved in several biological processes, including tumor growth, angiogenesis, and invasiveness. However, the specific role of the NFAT1 family member in naive B cell proliferation remains elusive. Here, we demonstrate that NFAT1 transcription factor controls Cyclin E expression, cell proliferation, and tumor growth in vivo. Specifically, we show that inducible expression of NFAT1 inhibits cell cycle progression, reduces colony formation, and controls tumor growth in nude mice. We also demonstrate that NFAT1-deficient naive B lymphocytes show a hyperproliferative phenotype and high levels of Cyclin E1 and E2 upon BCR stimulation when compared to wild-type B lymphocytes. NFAT1 transcription factor directly regulates Cyclin E expression in B cells, inhibiting the G1/S cell cycle phase transition. Bioinformatics analysis indicates that low levels of NFAT1 correlate with high expression of Cyclin E1 in different human cancers, including Diffuse Large B-cell Lymphomas (DLBCL). Together, our results demonstrate a repressor role for NFAT1 in cell cycle progression and Cyclin E expression in B lymphocytes, and suggest a potential function for NFAT1 protein in B cell malignancies.

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“…Mice with combinations of mutations that disrupt expression of two D-type cyclins simultaneously and resulting in the expression of only one D-type cyclin have also been generated (Ciemerych et al, 2002;Ciemerych and Sicinski, 2005). Of these double mutants (D1/D2 KO, D1/D3 KO and D2/D3 KO), only a fraction of mice expressing cyclin D3 (D1/D2 KO) survive up to adulthood, but male reproductive tract phenotypes of these mice are unknown (Ciemerych et al, 2002;Ciemerych and Sicinski, 2005).…”

Section: Discussionmentioning

confidence: 99%

Segment- And Cell-Specific Expression of Dtype Cyclins in the Postnatal Mouse Epididymis

Wang

2007

Biology of Reproduction

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Sperm transport, maturation and storage are the essential functions of the epididymis. The epididymis in the mouse is structurally characterized by regional and segmental organization including caput, corpus and cauda epididymis that are comprised of ten segments. Although several growth factor signaling pathways have been discovered in the epididymis, how these converge onto the cell cycle components is unknown. To begin to elucidate the growth factor control of cell cycle events in the epididymis, we analyzed the expression of D-type cyclins at different postnatal ages. At 7d, cyclin D1 was mainly expressed in the cauda epithelium, by 14d its expression occurred in the epithelium of caput, corpus and cauda that persisted up to 21d. By 42d, cyclin D1 was mostly detectable in the principal cells of the caput and corpus (segments 1-7) but not in the cauda epididymis. Expression of cyclin D2, unlike that of cyclin D1, was evident only at 42d but not earlier, and was mostly confined to corpus and cauda epithelium. In contrast to both cyclin D1 and D2, cyclin D3 was expressed primarily in the interstitium at 7d and by 21d its expression was localized to the epithelium of the corpus and cauda epididymis. By 42d, expression of cyclin D3 peaked in segments 6-10 and confined to basal and principal cells of the corpus and apical cells of the cauda epithelium. Ki67 immunoreactivity confirmed absence of cell proliferation despite continued expression of D-type cyclins in the adult epididymis. Collectively, on the basis of our immunophenotyping and protein expression data, we conclude that the D-type cyclins are expressed in a development -, segment-, and cell-specific manner in the postnatal mouse epididymis.

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Cell cycle in mouse development

Cited by 146 publications

References 279 publications

Mammalian Mip/LIN-9 interacts with either the p107, p130/E2F4 repressor complex or B-Myb in a cell cycle-phase-dependent context distinct from the Drosophila dREAM complex

Mammalian Mip/LIN-9 interacts with either the p107, p130/E2F4 repressor complex or B-Myb in a cell cycle-phase-dependent context distinct from the Drosophila dREAM complex

NFAT1 transcription factor regulates cell cycle progression and cyclin E expression in B lymphocytes

Segment- And Cell-Specific Expression of Dtype Cyclins in the Postnatal Mouse Epididymis

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