Research

Area 5

Cell Proliferation and Signalling

Team manager
Oriol Bachs
(Facultat de Medicina)

Strategic objectives

The general objective of the group is to analyze the mechanisms that regulate cell proliferation and signalling in different experimental conditions and cell models. To achieve this goal, the group is developing 4 major lines of research:

1. Cell proliferation and cancer.
2. Cell signalling.
3. Signalling and regulation of the cell cycle.
4. Cell cycle: transduction of signals and checkpoints.

Main lines of research

1. Cell proliferation and cancer. The objective of this line of research is to analyze the mechanisms that control progression of the cell cycle and its alterations in oncogenesis. Specifically, we are studying the following:

  • The role of protein p27 in oncogenesis. There is evidence that reduced levels of p27 in tumors is linked to a poor outcome. The aim is to identify the role of p27 in tumor development.
  • The role of acetylation of proteins that regulate the cell cycle in the control of proliferation. The specific aim is to study the functional relevance of acetylation of p27, cyclin A and cdk2.
  • The role of the SET protein in oncogenesis. We are studying whether the role of this protein in the development of tumors is mediated by the phosphatase PP2A or by its phosphorylation by CK2.

2. Cell signalling. In this line of research, we study the molecular mechanisms of endocytosis, intracellular protein and cholesterol transport and the signalling processes in the endocytic compartment and the plasma membrane that may be involved in different diseases, such as those that cause accumulation of lipids and cholesterol or in cancer. Specifically, we are working on the aspects described below:

  • Role of annexin A6 in cell signalling. Analysis of the role of annexin A6 (a) in the formation of H-Ras-p120GAP complexes and in the inactivation of Ras and (b) in the transport of caveolin and in the formation of caveolae.
  • Biogenesis of lipid bodies. Study of the biogenesis of lipid bodies and their role in the transport of caveolin, intracellular accumulation of lipids and proliferative activation.
  • Role of calmodulin in the regulation of intracellular traffic of EGFR. Analysis of the role of calmodulin and of PKCd in the regulation of traffic and signalling and degradation of EGFR and transport of LDL through the early and late compartments of the endocytic compartment.

3. Signalling and regulation of the cell cycle. This line of research focuses on identification of the molecular mechanisms that regulate control of the cell cycle via the pathway of MAP kinases activated by stress in yeast cells and cultures of human normal and tumor cells. This research is divided into two lines of work:

  • Regulation of mitosis via the pathway of MAP kinases activated by stress in yeast cells. We aim to identify a) the mechanisms by which Srk1 regulates the restart of mitosis after blocking in phase G2 in response to stress, b) the specific components regulated by Srk1 in blocking the exit from mitosis produced by Srk1 and c) the molecular mechanisms by which Srk1 negatively regulates the activity of the p38/Sty1 kinase.
  • Regulation of mitosis via the pathway of MAP kinases activated by stress in cultures of normal and tumor cells. We aim to identify a) the mechanisms by which MK2 regulates the induction of apoptosis via the E2F1 transcription factor and b) new substrates of the MAPKAP-K2 kinase via the TAP purification system and proteomic analysis.

4. Cell cycle: transduction of signals and checkpoints. The objective of this line of work is to analyze the intracellular mechanisms of transduction of the signals that regulate the progression of the cell cycle and their control mechanisms or checkpoints. In relation to this general objective, in recent years, we have developed the following lines of research:

  • Regulation of the functionality of K-Ras by phosphorylation and binding to calmodulin. We aim to analyze the functional relevance of KRas and pre PKC and of the interaction with calmodulin.
  • Regulation of the functionality and intracellular location of p21Cip1 by phosphorylation and binding to calmodulin. We are currently analyzing the intracellular location of p21 in response to DNA damage and how its functionality may be regulated by phosphorylation or binding to calmodulin.
  • DNA replication checkpoint. We have shown that while colon cancer cells are fully dependent on ATR/ATM for inhibiting entry into mitosis in response to DNA synthesis inhibitors, the untransformed cells have parallel mechanisms, which allows them to better maintain the integrity of the genome when DNA replication problems occur.