Transcriptional role of cyclin D1 in development revealed by a genetic–proteomic screen

Bienvenu, Frédéric; Jirawatnotai, Siwanon; Elias, Joshua E.; Meyer, Clifford A.; Mizeracka, Karolina; Marson, Alexander; Frampton, Garrett M.; Cole, Megan F.; Odom, Duncan T.; Odajima, Junko; Geng, Yan; Zagożdżon, Agnieszka; Jecrois, Marie; Young, Richard A.; Liu, X. Shirley; Cepko, Constance L.; Gygi, Steven P.; Siciński, Piotr

doi:10.1038/nature08684

Cited by 248 publications

(259 citation statements)

References 30 publications

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“…Cdk1 can compensate for their combined loss by forming active complexes with A-, B-, E-, and D-type cyclins (6,24,27). Because constitutive inactivation of the Cdk1 locus led to early embryonic lethality, we had to resolve to generate a conditional knockout mouse model for detailed analysis of loss of Cdk1.…”

Section: Discussionmentioning

confidence: 99%

Cyclin-dependent kinase 1 (Cdk1) is essential for cell division and suppression of DNA re-replication but not for liver regeneration

Diril

Ratnacaram

Padmakumar

et al. 2012

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

323

324

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Cyclin-dependent kinase 1 (Cdk1) is an archetypical kinase and a central regulator that drives cells through G2 phase and mitosis. Knockouts of Cdk2, Cdk3, Cdk4, or Cdk6 have resulted in viable mice, but the in vivo functions of Cdk1 have not been fully explored in mammals. Here we have generated a conditional-knockout mouse model to study the functions of Cdk1 in vivo. Ablation of Cdk1 leads to arrest of embryonic development around the blastocyst stage. Interestingly, liver-specific deletion of Cdk1 is well tolerated, and liver regeneration after partial hepatectomy is not impaired, indicating that regeneration can be driven by cell growth without cell division. The loss of Cdk1 does not affect S phase progression but results in DNA re-replication because of an increase in Cdk2/cyclin A2 activity. Unlike other Cdks, loss of Cdk1 in the liver confers complete resistance against tumorigenesis induced by activated Ras and silencing of p53.cancer | knockout mice | cell cycle regulation | polyploidy

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Section: Discussionmentioning

confidence: 99%

Cyclin-dependent kinase 1 (Cdk1) is essential for cell division and suppression of DNA re-replication but not for liver regeneration

Diril

Ratnacaram

Padmakumar

et al. 2012

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

323

324

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“…There are many other reports showing that cell cycle regulators may function as cell fate determinants by a role independent of cell cycle regulation. 20,21,43,44 Furthermore, another detailed analysis suggests that not only G 1 -phase but also S-phase is correlated with the differentiation state of NSPCs. 38 Thus, the physiological functions of cyclin D2 in aspects of fate determination in vivo still remain to be elucidated.…”

Section: Cyclin D2 and Mammalianmentioning

confidence: 99%

How to keep proliferative neural stem/progenitor cells

Tsunekawa

Osumi

2012

Cell Cycle

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I t has long been argued that cell cycle regulators such as cyclins, cyclindependent kinases and their inhibitors affect the fate of neuronal progenitor cells. Recently, we identified that cyclin D2, which localizes at the basal tip of the radial glial cell (i.e., the neural progenitor in the developing neocortex), functions to give differential cell fates to its daughter cells just after cell division. This basally biased localization is due to transportation of cyclin D2 mRNA via its unique cis-regulatory sequence and local translation into cyclin D2 protein at the basal endfoot. During division of the neural progenitor cells, cyclin D2 protein is inherited by the daughter cell that retain the basal process, resulting in asymmetric distribution of cyclin D2 protein between the two daughter cells. Cyclin D2 is similarly localized in the human fetal cortical primordium, suggesting a common mechanism for the maintenance of neural progenitors and a possible scenario in evolution of primate brains. Here we introduce our recent findings and discuss how cyclin D2 functions in mammalian brain development and evolution.

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“…The full repertoire of cyclin D1 functions in normal development and oncogenesis is unclear at present [25].…”

Section: Prediction Of Functional Effect Of Ccnd1 Snp (Rs678653)mentioning

confidence: 99%

Computational prediction of novel human miRNAs/miRNA target sites in correlation with SNP (rs678653) at 3’UTR of cyclin D1 gene

Thakur¹,

Basir²,

Bharadwaj³

et al. 2017

Integr Mol Med

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MicroRNAs (miRNAs) are an extensive class of small noncoding RNAs, having profound impact on many biological processes in development, differentiation, growth and metabolism by regulating gene expression. Polymorphism in 3'UTR showed to alter the miRNA binding site in several human genes and consequently affects the function of the resulting protein posttrancriptionally. To investigate the putative functional consequences of the Cyclin D1 (CCND1) G/C1722 SNP (rs678653) located on 3'UTR of the gene, in-silico approach was applied for the prediction of miRNA binding sites using miRDB version 3.0 & 5.0.We were able to predict 16 miRNA/miRNA target sites on 3'UTR of human CCND1 gene. Out of 16 predicted miRNAs 11 were novel miRNAs/miRNA target sites which target CCND1. However no miRNA target sites were predicted on the DNA/RNA sequence of 3'UTR of human CCND1 gene encompassing the SNP (rs678653). Hence, SNP (rs678653) is not likely to be of functional importance according to this algorithmic prediction. Further experimental analysis is required to validate this computational prediction for CCND1 variants.

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Transcriptional role of cyclin D1 in development revealed by a genetic–proteomic screen

Cited by 248 publications

References 30 publications

Cyclin-dependent kinase 1 (Cdk1) is essential for cell division and suppression of DNA re-replication but not for liver regeneration

Cyclin-dependent kinase 1 (Cdk1) is essential for cell division and suppression of DNA re-replication but not for liver regeneration

How to keep proliferative neural stem/progenitor cells

Computational prediction of novel human miRNAs/miRNA target sites in correlation with SNP (rs678653) at 3’UTR of cyclin D1 gene

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