Evidence map›Paper›PMID 40093074›Full record

ArticlebioRxiv : the preprint server for biology2025

Distinct allosteric networks in CDK4 and CDK6 in the cell cycle and in drug resistance.

Wengang Zhang, Devin Bradburn, Gretchen Heidebrink, Yonglan Liu, Hyunbum Jang, Ruth Nussinov, Mardo Kõivomägi

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Wengang ZhangCancer Innovation Laboratory, National Cancer Institute, Frederick, MD 21702, U.S.A.ORCID 0000-0001-9653-6966
Devin BradburnLaboratory of Biochemistry and Molecular Biology, National Cancer Institute, Bethesda, MD 20892, U.S.A.
Gretchen HeidebrinkLaboratory of Biochemistry and Molecular Biology, National Cancer Institute, Bethesda, MD 20892, U.S.A.
Yonglan LiuCancer Innovation Laboratory, National Cancer Institute, Frederick, MD 21702, U.S.A.
Hyunbum JangCancer Innovation Laboratory, National Cancer Institute, Frederick, MD 21702, U.S.A.
Ruth NussinovCancer Innovation Laboratory, National Cancer Institute, Frederick, MD 21702, U.S.A.
Mardo KõivomägiLaboratory of Biochemistry and Molecular Biology, National Cancer Institute, Bethesda, MD 20892, U.S.A.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cyclin-dependent kinases 4 and 6 (CDK4 and CDK6) are key regulators of the G1-S phase transition in the cell cycle. In cancer cells, CDK6 overexpression often outcompetes CDK4 in driving cell cycle progression, contributing to resistance against CDK4/6 inhibitors (CDK4/6i). This suggests distinct functional and conformational differences between these two kinases, despite their striking structural and sequence similarities. Understanding the mechanisms that differentiate CDK4 and CDK6 is crucial, as resistance to CDK4/6i-frequently linked to CDK6 overexpression-remains a significant therapeutic challenge. Notably, CDK6 is often upregulated in CDK4/6i-resistant cancers and rapidly proliferating hematopoietic stem cells, underscoring its unique regulatory roles. We hypothesize that their distinct conformational dynamics explain their differences in phosphorylation of retinoblastoma protein, Rb, inhibitor efficacy, and cell cycle control. This leads us to question

Indexed as

allosteric drug discoverycancerCDK inhibitorcyclin-dependent kinases (CDKs)G1 cell cycle phaseG1/S transitionligand binding

Identifiers

PMID40093074
PMCPMC11908124

What OpenQuestion holds

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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.