Evidence map›Paper›PMID 36882522›Full record

ArticleOncogene2023

CDK13 phosphorylates the translation machinery and promotes tumorigenic protein synthesis.

Chao Wu, Ting Xie, Ying Guo, Donghai Wang, Min Qiu, Ruyi Han, Guoliang Qing, Kaiwei Liang, Hudan Liu

Abstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
2.8field-weighted citation impact, top 10% 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

15 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 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

9 authors at 1 institution in 1 country.

Chao Wu *Department of Hematology, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, 430071, Wuhan, China.
Ting Xie *Department of Hematology, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, 430071, Wuhan, China.
Ying GuoFrontier Science Center of Immunology and Metabolism, Wuhan University, 430071, Wuhan, China.
Donghai WangFrontier Science Center of Immunology and Metabolism, Wuhan University, 430071, Wuhan, China.ORCID 0000-0001-6119-8557
Min QiuDepartment of Pathophysiology, School of Basic Medical Sciences, Wuhan University, 430071, Wuhan, China.
Ruyi HanFrontier Science Center of Immunology and Metabolism, Wuhan University, 430071, Wuhan, China.
Guoliang QingFrontier Science Center of Immunology and Metabolism, Wuhan University, 430071, Wuhan, China.ORCID 0000-0002-7892-2860
Kaiwei LiangDepartment of Pathophysiology, School of Basic Medical Sciences, Wuhan University, 430071, Wuhan, China.
Hudan LiuDepartment of Hematology, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, 430071, Wuhan, China. hudanliu@whu.edu.cn.ORCID 0000-0003-1362-6048
Wuhan University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cyclin-dependent kinase 13 (CDK13) has been suggested to phosphorylate RNA polymerase II and is involved in transcriptional activation. However, whether CDK13 catalyzes other protein substrates and how CDK13 contributes to tumorigenesis remain largely unclear. We here identify key translation machinery components, 4E-BP1 and eIF4B, as novel CDK13 substrates. CDK13 directly phosphorylates 4E-BP1 at Thr46 and eIF4B at Ser422; genetically or pharmacologically inhibiting CDK13 disrupts mRNA translation. Polysome profiling analysis shows that MYC oncoprotein synthesis strictly depends on CDK13-regulated translation in colorectal cancer (CRC), and CDK13 is required for CRC cell proliferation. As mTORC1 is implicated in 4E-BP1 and eIF4B phosphorylation, inactivation of CDK13 in combination with the mTORC1 inhibitor rapamycin further dephosphorylates 4E-BP1 and eIF4B and blocks protein synthesis. As a result, dual inhibition of CDK13 and mTORC1 induces more profound tumor cell death. These findings clarify the pro-tumorigenic role of CDK13 by direct phosphorylation of translation initiation factors and enhancing protein synthesis. Therefore, therapeutic targeting of CDK13 alone or in combination with rapamycin may pave a new way for cancer treatment.

Indexed as

Cell Cycle ProteinsPhosphoproteinsCarcinogenesisCDC2 Protein KinaseHumansMechanistic Target of Rapamycin Complex 1PhosphorylationProtein BiosynthesisSirolimusCDC2 Protein KinaseCDK13 protein, humanCell Cycle ProteinsMechanistic Target of Rapamycin Complex 1PhosphoproteinsSirolimus

Identifiers

PMID36882522
OpenAlexW4323356638

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.