Evidence map›Paper›PMID 16936279›Full record

ArticleThe American journal of pathology2006

Limited redundancy in phosphorylation of retinoblastoma tumor suppressor protein by cyclin-dependent kinases in acute lymphoblastic leukemia.

Nicole M R Schmitz, Andreas Hirt, Markus Aebi, Kurt Leibundgut

Open access · bronzeAbstract readComparative Study
In one paragraph

Article in The American journal of pathology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.3field-weighted citation impact, top 40% 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

11 citing papers in PubMed, 15 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

4 authors at 3 institutions in 1 country.

Nicole M R SchmitzDepartment of Clinical Research, University of Bern, and the Department of Paediatrics, University Children's Hospital Inselspital, Switzerland. N.M.Schmitz@bham.ac.uk
Andreas Hirt
Markus Aebi
Kurt Leibundgut
University Children’s Hospital Bern · CHÉcole Polytechnique Fédérale de Lausanne · CHUniversity Hospital of Bern · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cyclin-dependent kinases (CDKs) successively phosphorylate the retinoblastoma protein (RB) at the restriction point in G1 phase. Hyperphosphorylation results in functional inactivation of RB, activation of the E2F transcriptional program, and entry of cells into S phase. RB unphosphorylated at serine 608 has growth suppressive activity. Phosphorylation of serines 608/612 inhibits binding of E2F-1 to RB. In Nalm-6 acute lymphoblastic leukemia extracts, serine 608 is phosphorylated by CDK4/6 complexes but not by CDK2. We reasoned that phosphorylation of serines 608/612 by redundant CDKs could accelerate phospho group formation and determined which G1 CDK contributes to serine 612 phosphorylation. Here, we report that CDK4 complexes from Nalm-6 extracts phosphorylated in vitro the CDK2-preferred serine 612, which was inhibited by p16INK4a, and fascaplysin. In contrast, serine 780 and serine 795 were efficiently phosphorylated by CDK4 but not by CDK2. The data suggest that the redundancy in phosphorylation of RB by CDK2 and CDK4 in Nalm-6 extracts is limited. Serine 612 phosphorylation by CDK4 also occurred in extracts of childhood acute lymphoblastic leukemia cells but not in extracts of mobilized CD34+ hemopoietic progenitor cells. This phenomenon could contribute to the commitment of childhood acute lymphocytic leukemia cells to proliferate and explain their refractoriness to differentiation-inducing agents.

Indexed as

Protein Processing, Post-TranslationalAntigens, CD34Burkitt LymphomaCarbolinesCell DifferentiationCell-Free SystemCell Line, TumorCyclin-Dependent Kinase 2Cyclin-Dependent Kinase 4Drug Resistance, NeoplasmG1 PhaseHematopoietic Stem CellsHumansIndolesIndolizinesMultiprotein ComplexesAntigens, CD34CarbolinesCDK2 protein, humanCDK4 protein, humanCyclin-Dependent Kinase 2Cyclin-Dependent Kinase 4fascaplysineIndolesIndolizinesMultiprotein ComplexesQuaternary Ammonium CompoundsRetinoblastoma-Like Protein p107

Identifiers

PMID16936279
PMCPMC1698824
OpenAlexW2033479018

What OpenQuestion holds

Textmetadata
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.