Evidence map›Paper›PMID 30982746›Full record

ArticleMolecular cell2019

Cyclin D-Cdk4,6 Drives Cell-Cycle Progression via the Retinoblastoma Protein's C-Terminal Helix.

Benjamin R Topacio, Evgeny Zatulovskiy, Sandra Cristea, Shicong Xie, Carrie S Tambo, Seth M Rubin, Julien Sage, Mardo Kõivomägi, Jan M Skotheim

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 191 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
191citing papers in PubMed, 2 pooled it
13.1field-weighted citation impact, top 1% 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

191 citing papers in PubMed, 2 syntheses or guidelines pooled it, 285 citations in OpenAlex.

  1. Pooled it
  2. Prognostic and Predictive Value ofFrontiers in endocrinology · 2022
    Pooled it
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  19. Chromatin association promotes UBR5-mediated degradation of Rb.bioRxiv : the preprint server for biology · 2026
    Article
  20. Review

131 more citing papers are in PubMed but not listed here.

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

9 authors at 2 institutions in 1 country.

Benjamin R TopacioDepartment of Biology, Stanford University, Stanford, CA 94305, USA.
Evgeny ZatulovskiyDepartment of Biology, Stanford University, Stanford, CA 94305, USA.
Sandra CristeaDepartment of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Shicong XieDepartment of Biology, Stanford University, Stanford, CA 94305, USA.
Carrie S TamboDepartment of Chemistry and Biochemistry, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
Seth M RubinDepartment of Chemistry and Biochemistry, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
Julien SageDepartment of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Mardo KõivomägiDepartment of Biology, Stanford University, Stanford, CA 94305, USA. Electronic address: mardok@stanford.edu.
Jan M SkotheimDepartment of Biology, Stanford University, Stanford, CA 94305, USA. Electronic address: skotheim@stanford.edu.
Stanford University · USUniversity of California, Santa Cruz · US

Funding

Translational Oncology Research Program (Project-005)P30CA124435 · NCI · STANFORD UNIVERSITY · PI Melinda L. Telli · 2007 to 2026
$71.4M
Leveraging innovative technologies in basic and clinical cancer researchT32CA009302 · NCI · STANFORD UNIVERSITY · PI LAURA D ATTARDI, Aaron M Newman · 1985 to 2026
$19.1M
Mechanisms of restriction point response to dynamic growth factor signalsR01GM092925 · NIGMS · STANFORD UNIVERSITY · PI SKOTHEIM, JAN M · 2010 to 2018
$2.8M
Determining the molecular mechanism of cell size controlR01GM115479 · NIGMS · STANFORD UNIVERSITY · PI SKOTHEIM, JAN M · 2016 to 2019
$1.6M
BD Canto II RUO CytometerS10RR027431 · NCRR · STANFORD UNIVERSITY · PI NOLAN, GARRY P · 2010 to 2010
$236k
NCI NIH HHS P30 CA124435NCI NIH HHS T32 CA009302NCRR NIH HHS S10 RR027431NIGMS NIH HHS R01 GM092925NIGMS NIH HHS R01 GM115479
6 · The paper itself

Abstract

The cyclin-dependent kinases Cdk4 and Cdk6 form complexes with D-type cyclins to drive cell proliferation. A well-known target of cyclin D-Cdk4,6 is the retinoblastoma protein Rb, which inhibits cell-cycle progression until its inactivation by phosphorylation. However, the role of Rb phosphorylation by cyclin D-Cdk4,6 in cell-cycle progression is unclear because Rb can be phosphorylated by other cyclin-Cdks, and cyclin D-Cdk4,6 has other targets involved in cell division. Here, we show that cyclin D-Cdk4,6 docks one side of an alpha-helix in the Rb C terminus, which is not recognized by cyclins E, A, and B. This helix-based docking mechanism is shared by the p107 and p130 Rb-family members across metazoans. Mutation of the Rb C-terminal helix prevents its phosphorylation, promotes G1 arrest, and enhances Rb's tumor suppressive function. Our work conclusively demonstrates that the cyclin D-Rb interaction drives cell division and expands the diversity of known cyclin-based protein docking mechanisms.

Indexed as

Cell CycleCell ProliferationCrk-Associated Substrate ProteinCyclin DCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6CyclinsG1 PhaseHumansMolecular Docking SimulationPhosphorylationProtein BindingProtein Conformation, alpha-HelicalProtein Interaction MapsRetinoblastoma-Like Protein p107Retinoblastoma ProteinBCAR1 protein, humanCrk-Associated Substrate ProteinCyclin DCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6CyclinsRetinoblastoma-Like Protein p107Retinoblastoma ProteinCdkcell-cycle regulationcyclindockingE2FG1/SkinasephosphorylationRb

Identifiers

PMID30982746
PMCPMC6800134
OpenAlexW2952456576

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.