DOI: 10.1073/pnas.0604320103. Genome-wide functional analysis of human cell-cycle regulators

Genome-wide functional analysis of human cell-cycle regulators

10.1073/pnas.0604320103

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Human cells have evolved complex signaling networks to coordinate the cell cycle. A detailed understanding of the global regulation of this fundamental process requires comprehensive identification of the genes and pathways involved in the various stages of cell-cycle progression. To this end, we report a genome-wide analysis of the human cell cycle, cell size, and proliferation by targeting >95% of the protein-coding genes in the human genome using small interfering RNAs (siRNAs). Analysis of >2 million images, acquired by quantitative fluorescence microscopy, showed that depletion of 1,152 genes strongly affected cell-cycle progression. These genes clustered into eight distinct phenotypic categories based on phase of arrest, nuclear area, and nuclear morphology. Phase-specific networks were built by interrogating knowledge-based and physical interaction databases with identified genes. Genome-wide analysis of cell-cycle regulators revealed a number of kinase, phosphatase, and proteolytic proteins and also suggests that processes thought to regulate G 1 -S phase progression like receptor-mediated signaling, nutrient status, and translation also play important roles in the regulation of G 2 /M phase transition. Moreover, 15 genes that are integral to TNF/NF-κB signaling were found to regulate G 2 /M, a previously unanticipated role for this pathway. These analyses provide systems-level insight into both known and novel genes as well as pathways that regulate cell-cycle progression, a number of which may provide new therapeutic approaches for the treatment of cancer.

Bibliography

Mukherji, M., Bell, R., Supekova, L., Wang, Y., Orth, A. P., Batalov, S., Miraglia, L., Huesken, D., Lange, J., Martin, C., Sahasrabudhe, S., Reinhardt, M., Natt, F., Hall, J., Mickanin, C., Labow, M., Chanda, S. K., Cho, C. Y., & Schultz, P. G. (2006). Genome-wide functional analysis of human cell-cycle regulators. Proceedings of the National Academy of Sciences, 103(40), 14819â14824.

Authors 19

Mridul Mukherji (first)
Russell Bell (additional)
Lubica Supekova (additional)
Yan Wang (additional)
Anthony P. Orth (additional)
Serge Batalov (additional)
Loren Miraglia (additional)
Dieter Huesken (additional)
Joerg Lange (additional)
Christopher Martin (additional)
Sudhir Sahasrabudhe (additional)
Mischa Reinhardt (additional)
Francois Natt (additional)
Jonathan Hall (additional)
Craig Mickanin (additional)
Mark Labow (additional)
Sumit K. Chanda (additional)
Charles Y. Cho (additional)
Peter G. Schultz (additional)

References 35 Referenced 113

Dates

Type	When
Created	18 years, 11 months ago (Sept. 25, 2006, 9:03 p.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 3:48 p.m.)
Indexed	2 months, 2 weeks ago (June 11, 2025, 11:05 a.m.)
Issued	18 years, 10 months ago (Oct. 3, 2006)
Published	18 years, 10 months ago (Oct. 3, 2006)
Published Online	18 years, 10 months ago (Oct. 3, 2006)
Published Print	18 years, 10 months ago (Oct. 3, 2006)

Funders 0

None

BibTeX

@article{Mukherji_2006, title={Genome-wide functional analysis of human cell-cycle regulators}, volume={103}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0604320103}, DOI={10.1073/pnas.0604320103}, number={40}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Mukherji, Mridul and Bell, Russell and Supekova, Lubica and Wang, Yan and Orth, Anthony P. and Batalov, Serge and Miraglia, Loren and Huesken, Dieter and Lange, Joerg and Martin, Christopher and Sahasrabudhe, Sudhir and Reinhardt, Mischa and Natt, Francois and Hall, Jonathan and Mickanin, Craig and Labow, Mark and Chanda, Sumit K. and Cho, Charles Y. and Schultz, Peter G.}, year={2006}, month=oct, pages={14819–14824} }

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