A cyclin without cyclin-dependent kinases: cyclin F controls genome stability through ubiquitin-mediated proteolysis

D’Angiolella, Vincenzo; Esencay, Mine; Pagano, Michele

doi:10.1016/j.tcb.2012.10.011

Cited by 89 publications

(91 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This interaction appears to be mediated via the cyclin box domain of cyclin F, which directs cyclin F protein substrates for ubiquitiylation and subsequent degradation 5 . Notably, B-Myb harbours multiple cyclin-binding sites (Cy-motifs) dispersed throughout the entire sequence, and consistent with this, we were unable to map a single B-Myb region required for the interaction with cyclin F. On the basis of this, we now propose that B-Myb makes multiple independent Cy-motif-based contacts with cyclin F. Intriguingly, we have so far not identified a role for cyclin F-mediated protein turnover in checkpoint control, and although protein degradation remains a contributing possibility, we favour alternative mechanistic explanations for the role of cyclin F. First, we propose that cyclin F may directly compete with cyclin A for binding to B-Myb, thereby suppressing B-Myb phosphorylation and activation.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Cyclin F suppresses B-Myb activity to promote cell cycle checkpoint control

et al. 2015

View full text Add to dashboard Cite

Cells respond to DNA damage by activating cell cycle checkpoints to delay proliferation and facilitate DNA repair. Here, to uncover new checkpoint regulators, we perform RNA interference screening targeting genes involved in ubiquitylation processes. We show that the F-box protein cyclin F plays an important role in checkpoint control following ionizing radiation. Cyclin F-depleted cells initiate checkpoint signalling after ionizing radiation, but fail to maintain G2 phase arrest and progress into mitosis prematurely. Importantly, cyclin F suppresses the B-Myb-driven transcriptional programme that promotes accumulation of crucial mitosis-promoting proteins. Cyclin F interacts with B-Myb via the cyclin box domain. This interaction is important to suppress cyclin A-mediated phosphorylation of B-Myb, a key step in B-Myb activation. In summary, we uncover a regulatory mechanism linking the F-box protein cyclin F with suppression of the B-Myb/cyclin A pathway to ensure a DNA damage-induced checkpoint response in G2.

show abstract

Section: Discussionmentioning

confidence: 99%

“…An emerging factor in genome maintenance is cyclin F, which is not a bona fide CDK-activating cyclin, but an F-box protein belonging to the Skp1-Cullin-F-box (SCF) ubiquitin ligase type family 5 . Previously, NUSAP1 and RRM2 have been described as cyclin F substrates 6,7 .…”

mentioning

confidence: 99%

Cyclin F suppresses B-Myb activity to promote cell cycle checkpoint control

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Because the cyclin box forms the substrate recognition module, cyclin F recruits substrates to SCF for ubiquitylation in a manner analogous to cyclins bringing substrates to Cdk for phosphorylation (Fig. 6) (D'Angiolella et al, 2013). Unlike other F-box proteins, which require prior phosphorylation to bind substrates, this distinctive mode of substrate recognition enables cyclin F to target a different subset of proteins.…”

Section: Cdks Cyclins and Ckis Regulating Proteolytic Degradationmentioning

confidence: 99%

Cdks, cyclins and CKIs: roles beyond cell cycle regulation

2013

View full text Add to dashboard Cite

SummaryCyclin-dependent kinases (Cdks) are serine/threonine kinases and their catalytic activities are modulated by interactions with cyclins and Cdk inhibitors (CKIs). Close cooperation between this trio is necessary for ensuring orderly progression through the cell cycle. In addition to their well-established function in cell cycle control, it is becoming increasingly apparent that mammalian Cdks, cyclins and CKIs play indispensable roles in processes such as transcription, epigenetic regulation, metabolism, stem cell self-renewal, neuronal functions and spermatogenesis. Even more remarkably, they can accomplish some of these tasks individually, without the need for Cdk/cyclin complex formation or kinase activity. In this Review, we discuss the latest revelations about Cdks, cyclins and CKIs with the goal of showcasing their functional diversity beyond cell cycle regulation and their impact on development and disease in mammals.

show abstract

“…35 A role for this pathway in genome instability and DNA damage has been recently reported. 36 The full details of biological process and pathway enrichment are provided in Table S2.…”

Section: Binding Site Characteristicsmentioning

confidence: 99%

High-throughput analyses of hnRNP H1 dissects its multi-functional aspect

et al. 2016

View full text Add to dashboard Cite

ABSTRACThnRNPs are polyvalent RNA binding proteins that have been implicated in a range of regulatory roles including splicing, mRNA decay, translation, and miRNA metabolism. A variety of genome wide studies have taken advantage of methods like CLIP and RIP to identify the targets and binding sites of RNA binding proteins. However, due to the complex nature of RNA-binding proteins, these studies are incomplete without assays that characterize the impact of RBP binding on mRNA target expression. Here we used a suite of high-throughput approaches (RIP-Seq, iCLIP, RNA-Seq and shotgun proteomics) to provide a comprehensive view of hnRNP H1s ensemble of targets and its role in splicing, mRNA decay, and translation. The combination of RIP-Seq and iCLIP allowed us to identify a set of 1,086 high confidence target transcripts. Binding site motif analysis of these targets suggests the TGGG tetramer as a prevalent component of hnRNP H1 binding motif, with particular enrichment around intronic hnRNP H1 sites. Our analysis of the target transcripts and binding sites indicates that hnRNP H1s involvement in splicing is 2-fold: it directly affects a substantial number of splicing events, but also regulates the expression of major components of the splicing machinery and other RBPs with known roles in splicing regulation. The identified mRNA targets displayed function enrichment in MAPK signaling and ubiquitin mediated proteolysis, which might be main routes by which hnRNP H1 promotes tumorigenesis.

show abstract

A cyclin without cyclin-dependent kinases: cyclin F controls genome stability through ubiquitin-mediated proteolysis

Cited by 89 publications

References 50 publications

Cyclin F suppresses B-Myb activity to promote cell cycle checkpoint control

Cyclin F suppresses B-Myb activity to promote cell cycle checkpoint control

Cdks, cyclins and CKIs: roles beyond cell cycle regulation

High-throughput analyses of hnRNP H1 dissects its multi-functional aspect

Contact Info

Product

Resources

About