Evidence map›Paper›PMID 26929199›Full record

ArticleMolecular and cellular biology2016

Phosphorylation-Dependent Regulation of the DNA Damage Response of Adaptor Protein KIBRA in Cancer Cells.

Jayadev Mavuluri, Swarnalatha Beesetti, Rohan Surabhi, Joachim Kremerskothen, Ganesh Venkatraman, Suresh K Rayala

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular and cellular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.2field-weighted citation impact, top 20% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 14 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 2 countries.

Jayadev MavuluriDepartment of Biotechnology, Indian Institute of Technology Madras (IITM), Chennai, India.
Swarnalatha BeesettiDepartment of Biotechnology, Indian Institute of Technology Madras (IITM), Chennai, India.
Rohan SurabhiDepartment of Biotechnology, Indian Institute of Technology Madras (IITM), Chennai, India Departments of Human Genetics, Sri Ramachandra University, Porur, Chennai, India.
Joachim KremerskothenDepartment of Nephrology, Hypertension and Rheumatology, University Hospital Muenster, Muenster, Germany.
Ganesh VenkatramanDepartments of Human Genetics, Sri Ramachandra University, Porur, Chennai, India ganeshv@sriramachandra.edu.in rayala@iitm.ac.in.
Suresh K RayalaDepartment of Biotechnology, Indian Institute of Technology Madras (IITM), Chennai, India ganeshv@sriramachandra.edu.in rayala@iitm.ac.in.
Indian Institute of Technology Madras · INSri Ramachandra Institute of Higher Education and Research · INUniversity Hospital Münster · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Multifunctional adaptor proteins encompassing various protein-protein interaction domains play a central role in the DNA damage response pathway. In this report, we show that KIBRA is a physiologically interacting reversible substrate of ataxia telangiectasia mutated (ATM) kinase. We identified the site of phosphorylation in KIBRA as threonine 1006, which is embedded within the serine/threonine (S/T) Q consensus motif, by site-directed mutagenesis, and we further confirmed the same with a phospho-(S/T) Q motif-specific antibody. Results from DNA repair functional assays such as the γ-H2AX assay, pulsed-field gel electrophoresis (PFGE), Comet assay, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assay, and clonogenic cell survival assay using stable overexpression clones of wild-type (wt.) KIBRA and active (T1006E) and inactive (T1006A) KIBRA phosphorylation mutants showed that T1006 phosphorylation on KIBRA is essential for optimal DNA double-strand break repair in cancer cells. Further, results from stable retroviral short hairpin RNA-mediated knockdown (KD) clones of KIBRA and KIBRA knockout (KO) model cells generated by a clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 system showed that depleting KIBRA levels compromised the DNA repair functions in cancer cells upon inducing DNA damage. All these phenotypic events were reversed upon reconstitution of KIBRA into cells lacking KIBRA knock-in (KI) model cells. All these results point to the fact that phosphorylated KIBRA might be functioning as a scaffolding protein/adaptor protein facilitating the platform for further recruitment of other DNA damage response factors. In summary, these data demonstrate the imperative functional role of KIBRAper se(KIBRA phosphorylation at T1006 site as a molecular switch that regulates the DNA damage response, possibly via the nonhomologous end joining [NHEJ] pathway), suggesting that KIBRA could be a potential therapeutic target for modulating chemoresistance in cancer cells.

Indexed as

Ataxia Telangiectasia Mutated ProteinsBleomycinBreast NeoplasmsCell Line, TumorDNA Breaks, Double-StrandedDNA DamageDNA RepairDrug Resistance, NeoplasmFemaleGene Knockout TechniquesHumansIntracellular Signaling Peptides and ProteinsPhosphoproteinsPhosphorylationAtaxia Telangiectasia Mutated ProteinsATM protein, humanBleomycinIntracellular Signaling Peptides and ProteinsPhosphoproteinsWWC1 protein, human

Identifiers

PMID26929199
PMCPMC4836221
OpenAlexW2291611780

What OpenQuestion holds

Textmetadata
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.