Cyclin-dependent kinases: a family portrait

Malumbres, Marcos; Harlow, E; Hunt, Tim; Hunter, Tony; Lahti, Jill M.; Manning, Gerard; Morgan, David; Tsai, Li‐Huei; Wolgemuth, Debra J.

doi:10.1038/ncb1109-1275

Cited by 385 publications

(315 citation statements)

References 10 publications

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“…The closest homologs of CDC28p in metazoans are Cdk1 and Cdk2. The general dogma is that Cdk2 complexes promote entry and progression through S phase while Cdk1 controls mitosis although Cdk1 can almost completely compensate for the loss of Cdk2 (Santamaría et al , 2007; Malumbres et al , 2009). In particular, Cdk2 was found to play an active role in DNA repair (Deans et al , 2006; Wohlbold et al , 2012).…”

Section: Discussionmentioning

confidence: 99%

The plant‐specific CDKB 1‐ CYCB 1 complex mediates homologous recombination repair in Arabidopsis

et al. 2016

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Upon DNA damage, cyclin‐dependent kinases (CDKs) are typically inhibited to block cell division. In many organisms, however, it has been found that CDK activity is required for DNA repair, especially for homology‐dependent repair (HR), resulting in the conundrum how mitotic arrest and repair can be reconciled. Here, we show that Arabidopsis thaliana solves this dilemma by a division of labor strategy. We identify the plant‐specific B1‐type CDKs (CDKB1s) and the class of B1‐type cyclins (CYCB1s) as major regulators of HR in plants. We find that RADIATION SENSITIVE 51 (RAD51), a core mediator of HR, is a substrate of CDKB1‐CYCB1 complexes. Conversely, mutants in CDKB1 and CYCB1 fail to recruit RAD51 to damaged DNA. CYCB1;1 is specifically activated after DNA damage and we show that this activation is directly controlled by SUPPRESSOR OF GAMMA RESPONSE 1 (SOG1), a transcription factor that acts similarly to p53 in animals. Thus, while the major mitotic cell‐cycle activity is blocked after DNA damage, CDKB1‐CYCB1 complexes are specifically activated to mediate HR.

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Section: Discussionmentioning

confidence: 99%

The plant‐specific CDKB 1‐ CYCB 1 complex mediates homologous recombination repair in Arabidopsis

et al. 2016

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“…[1][2][3] Dysregulation of CDKs and their regulatory partners, known as cyclins, disrupts proper control of cell proliferation, differentiation or apoptosis, thereby leading to abnormal development and diseases such as cancer. There are 21 CDK family members in mammals.…”

Section: Introductionmentioning

confidence: 99%

“…There are 21 CDK family members in mammals. [1][2][3] Many studies in the past three decades have provided significant insights into understanding the roles of several CDKs, such as CDK1, CDK2, CDK4 and CDK6, in regulating cell proliferation and how dysregulation of these CDKs and their regulatory cyclins contributes to tumorigenesis. 2,4,5 However, much less is known about the potential roles of other CDKs and their deregulation in human cancers and other diseases.…”

Section: Introductionmentioning

confidence: 99%

Tumor-suppressive effects of CDK8 in endometrial cancer cells

Wang

et al. 2013

Cell Cycle

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“…1,2 CDKs (CDK1-CDK6) mostly promote the progression from one cell-cycle phase to the next, and CDK1 is essential for proliferation. CDKs have been characterized extensively, and some of their substrates and in vivo functions are known.…”

Section: Introductionmentioning

confidence: 99%

CDK10 Mutations in Humans and Mice Cause Severe Growth Retardation, Spine Malformations, and Developmental Delays

Windpassinger

Piard

Bonnard

et al. 2017

The American Journal of Human Genetics

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In five separate families, we identified nine individuals affected by a previously unidentified syndrome characterized by growth retardation, spine malformation, facial dysmorphisms, and developmental delays. Using homozygosity mapping, array CGH, and exome sequencing, we uncovered bi-allelic loss-of-function CDK10 mutations segregating with this disease. CDK10 is a protein kinase that partners with cyclin M to phosphorylate substrates such as ETS2 and PKN2 in order to modulate cellular growth. To validate and model the pathogenicity of these CDK10 germline mutations, we generated conditional-knockout mice. Homozygous Cdk10-knockout mice died postnatally with severe growth retardation, skeletal defects, and kidney and lung abnormalities, symptoms that partly resemble the disease's effect in humans. Fibroblasts derived from affected individuals and Cdk10-knockout mouse embryonic fibroblasts (MEFs) proliferated normally; however, Cdk10-knockout MEFs developed longer cilia. Comparative transcriptomic analysis of mutant and wild-type mouse organs revealed lipid metabolic changes consistent with growth impairment and altered ciliogenesis in the absence of CDK10. Our results document the CDK10 loss-of-function phenotype and point to a function for CDK10 in transducing signals received at the primary cilia to sustain embryonic and postnatal development.

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Cyclin-dependent kinases: a family portrait

Cited by 385 publications

References 10 publications

The plant‐specific CDKB 1‐ CYCB 1 complex mediates homologous recombination repair in Arabidopsis

The plant‐specific CDKB 1‐ CYCB 1 complex mediates homologous recombination repair in Arabidopsis

Tumor-suppressive effects of CDK8 in endometrial cancer cells

CDK10 Mutations in Humans and Mice Cause Severe Growth Retardation, Spine Malformations, and Developmental Delays

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