Sergio Moreno

Cell growth, division and differentiation

The main interest of our group is to understand how cells coordinate cell growth and division with cell differentiation. To study this biological problem we use two model organisms, the fission yeast Schizosaccharomyces pombe, a unicellular organism widely used in cell cycle research, and the mouse, where we analyse the physio-pathological consequences of knocking down cell cycle regulator genes in animal cells.

In fission yeast, we have recently described that the greatwall-endosulfine (Ppk18-Igo1, in fission yeast) pathway couples the nutritional environment to the cell cycle machinery by regulating the activity of PP2A·B55. In the presence of nutrients, greatwall (Ppk18) protein kinase is inhibited by TORC1 and PP2A·B55 is active. High levels of PP2A·B55 prevent the activation of mitotic Cdk1·Cyclin B and cells increase in size in G2 before they undergo mitosis. When nutrients are limiting, TORC1 activity falls off and the activation of greatwall (Ppk18) leads to the phosphorylation of endosulfine (Igo1) and inhibition of PP2A·B55, which in turn allows full activation of Cdk1·CyclinB and entry into mitosis with a smaller cell size.

The greatwall-endosulfine-PP2A·B55 pathway regulates cell size by coupling cell growth (TORC1 activity) to the cell cycle machinery (Cdk1/CyclinB)

In mice we are studying the function of the Anaphase Promoting Complex or Cyclosome (APC/C) and its cofactor Cdh1, a E3 ubiquitin ligase that targets many substrates for proteosomal degradation during G1. Our preliminary results indicate that Cdh1-deficient MEFs accumulate DNA breaks and show slow replication fork progression and increased origin activation, consistent with replication stress. We are currently investigating the role of APC/C-Cdh1 in the prevention of replication stress and premature aging.

The Cdh1/Skp2/p27 pathway in cancer and cell differentiation

In G1, low the Cdk/cyclin activity is required for the correct assembly of pre-replication complexes and for cell cycle exit. This low Cdk activity is achived by the combined activity of APC/C-Cdh1 that promotes mitotic cyclin degradation and the Cdk inhibitors, p21 and p27. Skp2, one of the targets of APC/C-Cdh1, promotes the degradation of p21 and p27.

Group members
Natalia García-Blanco Master student
Irene García-Higuera AECC Postdoctoral
Daniel García-Ruano Undergraduate student
Irene González Valero Technician
Sergio Moreno Research Professor IP
Livia Pérez-Hidalgo Postdoctoral
Rubén Rodríguez PhD student
Ana Elisa Rozalén Technician
Angela Rubio PhD student
Sandra Ruibal Puertas Undergraduate student
Marta Tormos-Pérez PhD student
Alicia U. Vázquez Bolado PhD student
Recent publications
Chica N, Rozalén AE, Pérez-Hidalgo L, Rubio A, Novak B and Moreno S (2016)
Nutritional control of cell size by the greatwall-endosulfine-PP2A·B55 pathway
Current Biology 26: 319-330
Santos-Pereira JM, Herrero AB, García-Rubio ML, Marín A, Moreno S and Aguilera A (2013)
The Npl3 hnRNP prevents R-loop-mediated transcription-replication conflicts and genome instability
Genes and Development 27: 2445-2458
Delgado-Esteban M, García-Higuera I, Maestre C, Moreno S and Almeida A (2013)
APC/C-Cdh1 coordinates neurogenesis and cortical size during development
Nat. Commun.4: 2879
Valbuena N and Moreno S (2012)
AMPK phosphorylation by Ssp1 is required for proper sexual differentiation in fission yeast
J. Cell Sci.
125: 2655-2664
Valbuena N, Guan K-L and Moreno S (2012)
The Vam6-Gtr1/Gtr2 pathway activates TORC1 in response to amino acids in fission yeast
J. Cell Sci.
125: 1920-1928
Research grants
MINECO Red de Excelencia BFU2014-51672-REDC
MINECO BFU2014-55439-R
Links of interest
S. pombe database

S. pombe meiotic genes database

Consolider Inesgen

Máster en Biología y Clínica del Cáncer