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Pablo Lara-Gonzalez

@xtpablo.bsky.social

109 followers 174 following 13 posts

Assistant Professor at UC Irvine. Mitosis and C. elegans aficionado.

Pablo Lara-Gonzalez @xtpablo.bsky.social · 02/10/2026

5/ We also used phospho-mass spectrometry to identify substrates of cyclin B3 during mitosis. Overall, we identified cyclin B3 as a selective driver of cancer cell division, which could represent a mitotic vulnerability specific to cancer.

Proposed mechanism by which cyclin B3 drives cancer cell mitosis

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Pablo Lara-Gonzalez @xtpablo.bsky.social · 02/10/2026

4/ This function holds across multiple cancer cell lines from diverse origins. However, non-transformed (normal) cells are not affected by cyclin B3 depletion, consistent with the fact that cyclin B3 mutations don't appear to affect normal human development beyond oocyte maturation.

Quantification of mitotic timing in various normal and cancerous cell lines, either control or treated with siRNAs against cyclin B3

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Pablo Lara-Gonzalez @xtpablo.bsky.social · 02/10/2026

3/ Our data revealed that Cyclin B3 is not only expressed in mitotic HeLa cells, but it is also critical for the normal pace of mitosis and ensuring proper chromosome alignment and segregation.

Immunofluorescence images of cyclin B3 depleted cells, as well as quantification of mitotic chromosome alignment errors in cyclin B3 depleted cells

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Pablo Lara-Gonzalez @xtpablo.bsky.social · 02/10/2026

2/ Our work centers on cyclin B3, a meiotic B-type cyclin known for its essential role in promoting the completion of meiosis I in oocytes. However, it is assumed that this B-type cyclin does not play significant roles outside of female meiosis rupress.org/jcb/article/...

Images showing oocytes undergoing meiosis I under the specified conditions. Note that Ccnb3-/- oocytes arrest in meiosis I. Credit: DOI: 10.1083/jcb.201808091

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Pablo Lara-Gonzalez @xtpablo.bsky.social · 24/07/2026

We show that cyclin B3–CDK1 promotes multi-site OMA phosphorylation to generate phosphodegrons and ensure its timely degradation, to subsequently drive mRNA de-repression. (5/7)

In vitro kinase assay using purified OMA-2 and cyclin B3-CDK1 complexes

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Pablo Lara-Gonzalez @xtpablo.bsky.social · 24/07/2026

Looking into potential targets, we identified the OMA RNA-binding proteins, known repressors of translation that must be degraded to allow early gene expression, as targets of the cyclin B3–CDK1 complex during embryogenesis. (4/7)

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Pablo Lara-Gonzalez @xtpablo.bsky.social · 24/07/2026

In this new manuscript, we reveal a second function of the cyclin B3–CDK1 complex. The key? A separation-of-function mutant we engineered by disrupting its conserved phosphate-binding pocket. Pocket mutant cyclin B3 still supports mitosis but leads to penetrant embryonic lethality (3/7)

AlphaFold3 model of cyclin B3 in complex with CDK1 showing two key binding surfaces: hydrophobic patch (HP) and phosphate binding pocket (PBP), as well as alignments showing their evolutionary conservation

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Pablo Lara-Gonzalez @xtpablo.bsky.social · 24/07/2026

My lab has been interested in understanding the mechanisms that drive mitotic divisions. In 2024, we showed that cyclin B3 is a key driver of mitotic divisions in C. elegans by acting as a hyperactivator of CDK1. But it turns out that's only half the story. (2/7) rupress.org/jcb/article/...

Images showing C. elegans embryos with green microtubules and magenta chromosomes undergoing mitosis after being treated with RNAi against cyclin B1 or cyclin B3

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