Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Cyclin dependent kinase 5 (CDK5) regulates the circadian clock

ABSTRACT: We show that the cyclin-dependent kinase 5 (CDK5) regulates the mammalian circadian clock via phosphorylation of PER2. CDK5 phosphorylated PER2 at serine residue 394 (S394) as shown by an in vitro kinase assay.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

SUBMITTER: Joern Dengjel

LAB HEAD: Joern Dengjel

PROVIDER: PXD012068 | Pride | 2019-12-04

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Publications

Cyclin-dependent kinase 5 (CDK5) regulates the circadian clock.

Brenna Andrea A Olejniczak Iwona I Chavan Rohit R Ripperger Jürgen A JA Langmesser Sonja S Cameroni Elisabetta E Hu Zehan Z De Virgilio Claudio C Dengjel Jörn J Albrecht Urs U

eLife 20191105

Circadian oscillations emerge from transcriptional and post-translational feedback loops. An important step in generating rhythmicity is the translocation of clock components into the nucleus, which is regulated in many cases by kinases. In mammals, the kinase promoting the nuclear import of the key clock component Period 2 (PER2) is unknown. Here, we show that the cyclin-dependent kinase 5 (CDK5) regulates the mammalian circadian clock involving phosphorylation of PER2. Knock-down of <i>Cdk5</i ...[more]

PMID: 31687929

Similar Datasets

Cdk5 drives formation of heterogeneous pancreatic neuroendocrine tumors.

Project description:Pancreatic neuroendocrine tumors (PanNETs) are a heterogeneous population of neoplasms that arise from hormone-secreting islet cells of the pancreas and have increased markedly in incidence over the past four decades. Non-functional PanNETs, which occur more frequently than hormone-secreting tumors, are often not diagnosed until later stages of tumor development and have poorer prognoses. Development of successful therapeutics for PanNETs has been slow, partially due to a lack of diverse animal models for pre-clinical testing. Here, we report development of an inducible, conditional mouse model of PanNETs by using a bitransgenic system for regulated expression of the aberrant activator of Cdk5, p25, specifically in b-islet cells. This model produces a heterogeneous population of PanNETs that includes a subgroup of well-differentiated, non-functional tumors. The utility of this model is enhanced by ability to form tumor-derived allografts. Production of these tumors demonstrates the causative potential of aberrantly active Cdk5 for generation of PanNETs. Further, we show that human PanNETs express Cdk5 pathway components, are dependent on Cdk5 for growth, and share genetic and transcriptional overlap with the INS-p25OE model. This new model of PanNETs will facilitate molecular delineation of Cdk5-dependent PanNETs and the development of new targeted therapeutics.

2021-06-10 | GSE176448 | GEO

CDK5-dependent phosphorylation and nuclear translocation of TRIM59 promotes macroH2A1 ubiquitination and tumorigenicity

Project description:Despite the development of adjuvant therapies, glioblastoma (GBM) patients remain incurable and justify the urgent need of new therapies. CDK5 functions a critical role in GBM and is a potential target for GBM. However, the mechanism by which CDK5 promotes GBM tumorigenicity remains largely unknown. Here we identify TRIM59 as a substrate of CDK5. EGFR-activated CDK5 directly binds to and phosphorylates TRIM59, a ubiquitin ligase at serine 308, which recruits PIN1 for cis-trans isomerization of TRIM59, leading to TRIM59 binding to importin a5 and nuclear translocation. Nuclear TRIM59 induces ubiquitination and degradation of the tumor suppressive histone variant macroH2A1, leading to enhanced STAT3 signaling activation and tumorigenicity. These findings are confirmed by inhibition of CDK5-activated TRIM59 activity that results in suppression of intracranial tumor growth. Correlative expressions of the components of this pathway are clinically prognostic. Our findings suggest targeting CDK5/TRIM59 signaling axis as a putative strategy for treating GBM.

2019-08-11 | GSE130949 | GEO

Cdk5 regulates activity-dependent gene expression and dendrite development [cultured cortical neurons]

Project description:To investigate the molecular mechanism underlying activity-dependent dendrite development regulated by Cdk5, an unbiased microarray analysis was performed to identify activity-dependent genes differentially regulated in cortical neurons from E18 Cdk5-knockout embryos.

2015-12-11 | GSE68320 | GEO

CDK5 inhibition abrogates TNBC stem-cell property and enhances anti-PD-1 therapy

Project description:Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that shows high infiltration of cancer stem cells (CSCs), which correlates with poor clinical outcome. Here, we have demonstrated that an aberrant activation of CDK5/pho-PPARg axis associated with TNBC progression closely. CDK5 blockade sufficiently abrogates stemness transformation of TNBC cells, resulting in a significant inhibition of tumor metastatic progression. Moreover, CDK5 inhibitor Rosc attenuates CD44v+ BCSCs, hereby reversing immunosuppressive microenvironment and enhancing anti-PD-1 effects on TNBC. Mechanistically, CDK5/pho-PPARgaxis modulates the ESRP1 degradation via E3 ligase-like activity, leading to CD44 variant (CD44v) expression. Our finding indicates that CDK5 blockade could be a potent strategy to target CSCs in TNBC, and to increase the response to PD-1 blockade in TNBC therapy.

2022-06-18 | GSE132902 | GEO

Different gene expression between CDK5 knocking down and control colorectal cancer cell line HCT116

Project description:We sought to find out the molecular mechanism of CDK5 displayed in colorectal cancer. Microarray experiments were carried out to identify different gene expression between CDK5-knockdown HCT116 cell lines and Scramble HCT116 cell lines.

2016-05-05 | GSE81085 | GEO

CDK5 activates Hippo signaling to confer resistance to radiotherapy via upregulating TAZ in lung cancer

Project description:Tumor resistance to radiotherapy is a therapeutic challenge in the treatment of patients with lung cancer. Cyclin-dependent kinase 5 (CDK5) has been proposed to participate in cell proliferation, migration and invasion; drug resistance; and immune evasion. However, the functions and regulatory mechanisms of CDK5 in lung cancer radioresistance have not been investigated.SiRNAs and ShRNAs were used to knock down CDK5 in A549 and H1299 cells. The effects of CDK5 depletion on the tumorigenic behaviors of non-small cell lung cancer (NSCLC) cells were evaluated in vitro and in vivo. Gene expression was examined by RNA-seq and quantitative real-time PCR.

2021-04-30 | GSE148532 | GEO

Substrate selectivity for semisynthetic CK2 proteins

Project description:This SuperSeries is composed of the following subset Series: GSE33149: Substrate selectivity for semisynthetic CK2 proteins with various posttranslational modifications GSE33150: Substrate selectivity for semisynthetic CK2 proteins with Pin1 Refer to individual Series

2011-10-24 | E-GEOD-33151 | biostudies-arrayexpress

Project description:We found that LC3B is phosphorylated in vitro by STK3, STK4, NEK9, and PKCζ. To identify phosphorylation sites following in vitro phosphorylation, GST-LC3B was overexpressed in E. coli, purified using glutathione-Sepharose 4 Fast Flow beads and incubated in kinase assays with recombinant kinases or FLAG-tagged kinases immunopurified from transiently transfected HEK293 cells

2020-01-23 | PXD016681 | Pride

Use of the dTAG system in vivo to degrade CDK2 and CDK5 in adult mice and explore potential safety liabilities [Duodenum]

Project description:The degradation tag (dTAG) system for target protein degradation can remove proteins from biological systems without the drawbacks of some genetic methods, such as slow kinetics, lack of reversibility, low specificity, and the inability to titrate dosage. These drawbacks can make it difficult to compare toxicity resulting from genetic and pharmacological interventions, especially in vivo. Because the dTAG system has not been studied extensively in vivo, we explored the use of this system to study the physiological sequalae resulting from CDK2 or CDK5 degradation in adult mice. Mice with knock-in of the dTAG sequence onto the C-terminus of CDK2 and CDK5 were born at Mendelian ratios despite decreased CDK2 or CDK5 protein levels in comparison to wild-type mice. In bone marrow cells and duodenum organoids derived from these mice, treatment with the dTAG degrader dTAG-13 resulted in rapid and robust protein degradation but caused no appreciable change in viability or the transcriptome. Repeated delivery of dTAG-13 in vivo for toxicity studies proved challenging; we explored multiple formulations in an effort to maximize degradation while minimizing formulation-related toxicity. Degradation of CDK2 or CDK5 in all organs except the brain, where dTAG-13 likely did not cross the blood brain barrier, only caused microscopic changes in the testis of CDK2dTAG mice. These findings were corroborated with conditional CDK2 knockout in adult mice. Our results suggest that the dTAG system can provide robust protein degradation in vivo and that loss of CDK2 or CDK5 in adult mice causes no previously unknown phenotypes.

2023-05-28 | GSE226388 | GEO

Substrate selectivity for semisynthetic CK2 proteins with Pin1

Project description:Protein Ser/Thr kinase CK2 is involved in a myriad of cellular processes including cell growth and proliferation by phosphorylating hundreds of substrates, yet the regulation process of CK2 function is poorly understood. The CK2 catalytic subunit, CK2α, is phosphorylated at Thr344 and phosphorylation on the C-terminal tail of CK2α is required for interaction with Pin1 protein. The substrate selectivity for protein kinase CK2α was examined by performing kinase assays on protein microarrays spotted with 17,000 human proteins. Semisynthetic CK2α proteins were prepared to contain an unmodified C-terminal tail or phospho-Thr (pThr) at T344. These semisynthetic proteins were used to determine if the phosphorylation-dependent interaction of CK2α with Pin1 can modulate the substrate selectivity for CK2. The different semisynthetic CK2α proteins (unmodified and pThr344) were tested alone and in the presence of the recombinant Pin1 protein. Pin1 has been shown to interaction with CK2α only when CK2α is phoshorylated on its C-terminal site (including Thr344). In the study presented here, kinase assays were performed using two different semisynthetic CK2α proteins: unmodified C-terminal tail and phospho-Thr (pThr) at 344. The semisynthetic proteins were each tested alone and in the presence of the recombinant Pin1 protein. There were four different kinase conditions and each condition was performed in duplicate.

2011-10-24 | E-GEOD-33150 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data