OSCR

The FAM53C/DYRK1A axis regulates the G1/S transition of the cell cycle.

Overview

Authors: Taylar Hammond1,2, Jong Bin Choi1, Miles W Membreño3, Janos Demeter4,5, Roy Ng4,5, Debadrita Bhattacharya1, Thuyen N Nguyen1, Griffin G Hartmann1,2, Caterina I Colon1,2, Carine Bossard6, Jan M Skotheim2, Peter K Jackson4,5, Anca M Pasca1, Seth M Rubin3, Julien Sage1,7
ORCID iDs: Jong Bin Choi, Roy Ng, Debadrita Bhattacharya, Carine Bossard, Jan M Skotheim, Peter K Jackson, Anca M Pasca, Seth M Rubin, Julien Sage
  1. Departments of Pediatrics, Stanford University, Stanford, United States
  2. Department of Biology, Stanford University, Stanford, United States
  3. Department of Chemistry and Biochemistry, University of California, Santa Cruz, Santa Cruz, United States
  4. Department of Microbiology and Immunology, Stanford University, Stanford, United States
  5. Department of Pathology, Stanford University, Stanford, United States
  6. Biosplice Therapeutics Inc, TenaRx Inc, San Diego, United States
  7. Department of Genetics, Stanford University, Stanford, United States
Institutions: Stanford Medicine (United States); Stanford University (United States); University of California, Santa Cruz (United States)
Journal: eLife, volume 14, article RP109708
Dates: published online 30 April 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.7554/elife.109708 · PMID 42059432 · PMCID PMC13132546 · OpenAlex W7114799703
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: human (organism), mouse (organism), cellular / molecular (subfield)
Methods: Statistics, Evoked potentials, Smoothing, state filtering, decompositions
Keywords: Mouse
MeSH: Cell Cycle Proteins*, Protein Serine-Threonine Kinases*, Protein-Tyrosine Kinases*, Animals, Cell Cycle, Dyrk Kinases, Humans, Mice, Mice, Knockout (* major topic)
Topic: Down syndrome and intellectual disability research (Public Health, Environmental and Occupational Health, Medicine), according to OpenAlex
Funding: NCI NIH HHS (P01 CA254867, P01CA254867)
Citations: cited by 1 paper (Europe PMC); 81 references in the paper

Abstract

A growing number of therapies are being developed to target the cell cycle machinery for the treatment of cancer and other human diseases. Consequently, a greater understanding of the factors regulating cell cycle progression becomes essential to help enhance the response to these new therapies. Here, using data from the Cancer Dependency Map, we identified FAM53C as a new regulator of cell cycle progression. We found that FAM53C is critical for this cell cycle transition and that it acts upstream of the Cyclin D-CDK4/6-RB axis and of p53 in the regulation of the G1/S transition. By mass spectrometry, biochemical, and cellular assays, we identified and validated DYRK1A as a cell cycle kinase that is inhibited by and directly interacts with FAM53C. Consistent with the role for FAM53C identified in cells in culture, FAM53C knockout human cortical organoids display increased cell cycle arrest and growth defects. Fam53C knockout mice show minor behavioral phenotypes. Because DYRK1A dysregulation contributes to developmental disorders such as Down syndrome as well as tumorigenesis, future strategies aiming at regulating FAM53C activity may benefit a broad range of patients.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

Tracing map

A tracing map links a paper to the code its authors published: this paper has none, so it has no map.

Data

Datasets cited

Data availability

Sequencing data from RNA sequencing are available from the Gene Expression Omnibus (GEO) under accession numbers GSE282945 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE282945). The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE (Vizcaíno et al., 2016) repository with the dataset identifier PXD055829 (10.6019/PXD055829 (https://doi.org/10.6019/PXD055829)). Data related to the IPMC genotyping and phenotyping of Fam53C mutant mice is available on the IPMC web sitewebsite. All other data and new material are available in the article and supplementary materials, at this link https://doi.org/10.5281/zenodo.19712495 (for source data), or from the corresponding author upon reasonable request.

The following datasets were generated:

Hammond T, Bhattacharya D, Sage J. 2025. The FAM53C/DYRK1A axis regulates the G1/S transition of the cell cycle. NCBI Gene Expression Omnibus. GSE282945

Demeter J, Jackson PK. 2026. The FAM53C/DYRK1A Axis Regulates The G1/S Transition Of The Cell Cycle. PRIDE. PXD055829

Sage J. 2026. Source Data for publication Hammond et al. Zenodo.

The following previously published dataset was used:

Arafeh R, Shibue T, Dempster JM. 2025. DepMap. Depmap.org.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 30 September 2026: the first record

Recorded: type, language, journal, volume, pages, dates, 15 authors, 1 keyword, 9 MeSH terms, 1 funder, 80 references.

Cite

This paper

Hammond, T., Choi, J. B., Membreño, M. W., Demeter, J., Ng, R., Bhattacharya, D., Nguyen, T. N., Hartmann, G. G., Colon, C. I., Bossard, C., Skotheim, J. M., Jackson, P. K., Pasca, A. M., Rubin, S. M., & Sage, J. (2026). The FAM53C/DYRK1A axis regulates the G1/S transition of the cell cycle. eLife, 14, RP109708. https://doi.org/10.7554/elife.109708

BibTeX

@article{hammond2026fam53c,
author = {Hammond, Taylar and Choi, Jong Bin and Membreño, Miles W and Demeter, Janos and Ng, Roy and Bhattacharya, Debadrita and Nguyen, Thuyen N and Hartmann, Griffin G and Colon, Caterina I and Bossard, Carine and Skotheim, Jan M and Jackson, Peter K and Pasca, Anca M and Rubin, Seth M and Sage, Julien},
title = {{The FAM53C/DYRK1A axis regulates the G1/S transition of the cell cycle}},
journal = {eLife},
year = {2026},
month = apr,
volume = {14},
pages = {RP109708},
publisher = {eLife Sciences Publications, Ltd},
issn = {2050-084X},
doi = {10.7554/elife.109708},
url = {https://doi.org/10.7554/elife.109708},
pmid = {42059432},
pmcid = {PMC13132546}
}

RIS

TY - JOUR
AU - Hammond, Taylar
AU - Choi, Jong Bin
AU - Membreño, Miles W
AU - Demeter, Janos
AU - Ng, Roy
AU - Bhattacharya, Debadrita
AU - Nguyen, Thuyen N
AU - Hartmann, Griffin G
AU - Colon, Caterina I
AU - Bossard, Carine
AU - Skotheim, Jan M
AU - Jackson, Peter K
AU - Pasca, Anca M
AU - Rubin, Seth M
AU - Sage, Julien
TI - The FAM53C/DYRK1A axis regulates the G1/S transition of the cell cycle
T2 - eLife
J2 - Elife
PY - 2026
DA - 2026/04/30
VL - 14
SP - RP109708
SN - 2050-084X
PB - eLife Sciences Publications, Ltd
DO - 10.7554/elife.109708
UR - https://doi.org/10.7554/elife.109708
LA - en
ER -

CSL-JSON

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