Lopez-Aviles group

Research Focus

Our group explores the regulation of cell cycle transitions by protein phosphatases using the fission yeast Schizosaccharomyces pombe as a model organism. Much of our work focuses on members of the PP2A family, which are frequently deregulated in cancer. In particular we are interested in recognizing their implication in the ordering of mitotic events as well as in the regulation of CDK activity during cell cycle exit and the G1 arrest that precedes differentiation. In addition, we have worked extensively in understanding how PP2A-B55 regulates the transcriptional landscape of proliferating and quiescent cells.

Another focus of interest in our group is the adaptative responses that control protein homeostasis during stress. We are currently working on the regulation of protein translation by a novel 4E-binding protein (4E-BP) in fission yeast. 

We aim to answer the following questions:

• What phosphatase(s) regulate CDK inactivation and exit from mitosis?
• What are the relevant substrates of PP2A-B55 that control the proliferation/differentiation switch? And how does dephosphorylation affect their genomic location/activity?
• What is the influence of 4E-BPs in the regulation of protein homeostasis during stress responses? And how is its activity controlled?

Current work:

• Current projects in the Lopez-Aviles Group

Techniques

We use a combination of classical genetic and cell biology techniques:

• Generation of conditional alleles, gene tagging, gene deletion and overexpression studies
• Genetic crosses, tetrad dissection and study of genetic interactions
• Multicopy suppressor screens of mutant situations
• Flow cytometry analysis
• Cell microscopy in fixed and living cells
• Molecular cloning
• Protein analysis by western blot
• Kinase and phosphatase assays
• Comparative proteomic and phosphoproteomic studies
• qPCR, RNA-Seq, ChIP-Seq

Selected publications

1. Marquina M, Lambea E, Carmona M, Sánchez-Marinas M, López-Aviles S, Ayte J, Hidalgo E, Aligue R. A new negative feedback mechanism for MAPK pathway inactivation through Srk1 MAPKAP kinase. Sci Rep. 2022 Nov 14;12(1):19501. doi: 10.1038/s41598-022-23970-8. PMID: 36376357; PMCID: PMC9663701.
2. Chica N, Portantier M, Nyquist-Andersen M, Espada-Burriel S, Lopez-Aviles S. Uncoupling of Mitosis and Cytokinesis Upon a Prolonged Arrest in Metaphase Is Influenced by Protein Phosphatases and Mitotic Transcription in Fission Yeast. Front Cell Dev Biol. 2022 Jul 18;10:876810. doi: 10.3389/fcell.2022.876810. PMID: 35923846; PMCID: PMC9340479.
3. Vilte Stonyte, Ruth Martín, Dario Segura-Peña, Nikolina Sekulić, Sandra Lopez-Aviles. (2020) Requirement of PP2A-B56^Par1 for the Stabilization of the CDK Inhibitor Rum1 and Activation of APC/C^Ste9 during Pre-Start G1 in S. pombe. iScience 23(5): 101063
4. Martin, R., Stonyte, V., Lopez-Aviles, S. (2020) Protein phosphatases in G1 regulation. International Journal of molecular sciences 21(2):395.
5. Shixiong Wang, Sachin Singh, Madhumohan Katika, Sandra Lopez-Aviles, Antoni Hurtado (2019) High Throughput Chemical Screening Reveals Multiple Regulatory Proteins on FOXA1 in Breast Cancer Cell Lines. International journal of molecular sciences 19(12): 4123.
6. Rothe, C., Rødland, G. E., Anda, S., Stonyte V., Boye, E., Lopez-Aviles, S. and Grallert, B. (2017) A checkpoint-independent mechanism delays entry into mitosis. Journal of Cell Science 130(23):4028-4037.
7. Martin, R., Portantier, M., Chica, N., Nyquist-Andersen, M., Mata, J., Lopez-Aviles, S. (2017) A PP2A-B55-mediated crosstalk between TORC1 and TORC2 regulates the differentiation response in fission yeast. Curr Biol 27(2): 175–188.
8. Martin R. and Lopez-Aviles, S. (2017) Express yourself: How PP2A helps TORC1 talk to TORC2. Current Genetics 2017 Jun 22.
9. Alba Gómez-Hierro, Eva Lambea, David Giménez-Zaragoza, Sandra Lopez-Aviles, Tula Yance-Chávez, Marta Montserrat, M. Jesús Pujol, Oriol Bachs, Rosa Aligue (2015). Ssp1 CaMKK: A Sensor of Actin Polarization That Controls Mitotic Commitment through Srk1 in Schizosaccharomyces pombe. PLoS One 10(11):e0143037.
10. Uhlmann, F. Bouchoux C and Lopez-Aviles, S. (2011). A quantitative model for Cdk control of the cell cycle, revisited. Phil. Trans. R. Soc. B
11. Lopez-Aviles, S., and Uhlmann, F. (2010). Cell cycle: the art of multi-tasking. Curr Biol 20, R101-103.
12. Kapuy, O., He, E., Lopez-Aviles, S., Uhlmann, F., Tyson, J.J., and Novak, B. (2009). System-level feedbacks control cell cycle progression. FEBS Lett 583, 3992-3998.
13. Lopez-Aviles, S., Kapuy, O., Novak, B., and Uhlmann, F. (2009). Irreversibility of mitotic exit is the consequence of systems-level feedback. Nature 459, 592-595.
14. Grande, M., Lambea, E., Fajardo, A., Lopez-Aviles, S., Kellogg, D., and Aligue, R. (2008). Crosstalk between Nap1 protein and Cds1 checkpoint kinase to maintain chromatin integrity. Biochim Biophys Acta 1783, 1595-1604.
15. Lopez-Aviles, S., Lambea, E., Moldon, A., Grande, M., Fajardo, A., Rodriguez-Gabriel, M.A., Hidalgo, E., and Aligue, R. (2008). Activation of Srk1 by the mitogen-activated protein kinase Sty1/Spc1 precedes its dissociation from the kinase and signals its degradation. Mol Biol Cell 19, 1670-1679.
16. Lopez-Aviles, S., Grande, M., Gonzalez, M., Helgesen, A.L., Alemany, V., Sanchez-Piris, M., Bachs, O., Millar, J.B., and Aligue, R. (2005). Inactivation of the Cdc25 phosphatase by the stress-activated Srk1 kinase in fission yeast. Mol Cell 17, 49-59.