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Noticia Científica I

Identification of a new protein involved in the modulation of the cell cycle

Cellular proliferation is essential during development and its strict regulation is also necessary to ensure the homeostasis of organs and tissues. Excessive proliferation independently of the presence of proliferative stimuli is one of the first steps in the complex process of the transformation of tumours.

The cell cycle comprises a series of temporally ordered and hierarchised mechanisms leading to the orderly growth of cells. The control mechanisms of the cell cycle (“cell-cycle checkpoints”) are especially important, responsible for preserving the fidelity of the copy of genetic material and its distribution to the child cells. When these mechanisms are not correctly activated when faced with factors threatening the integrity of DNA (chemical agents, radiation, etc), the cell cycle does not stop long enough to heal possible damage and/or eliminate damaged cells. This situation favours genomic instability and the progress of tumours.

The research team directed by Dr. Federico Mayor Menéndez and Dr. Petronila Penela Márquez of the “Severo Ochoa” Molecular Biology Centre (mixed centre of the Universidad Autónoma de Madrid and CSIC) has determined that the kinase of receptors coupled to G proteins, called GRK2, play a key role in the correct progress of the cell cycle and its control mechanisms.

The results of this study, published in the prestigious journal Proceedings of the National Academy of Sciences, show the reduction of cellular levels of GRK2 during a certain phase of the cell cycle (called G2) before mitosis. For this, a sequence of events is needed which enables the phases of the cycle to have a suitable duration, as if not the beginning of mitosis is delayed, due to the accumulation of GRK2.

The authors of the work have also shown that the treatment of the cells with doxorubicin, a genotoxic agent used in chemotherapy which damages DNA and activates the control mechanisms in phase G2/M, blocks the mechanism described above and causes the stabilisation of the GRK2 protein. This greater presence of GRK2 has two important consequences. On one hand it inhibits the induction of p53, which is a key factor in stress responses and which acts by executing apoptosis and cycle stopping routes. On the other, it promotes the cycle stopping (by mechanisms apparently independent of p53 which favour cellular survival).

Given that different oncogenic signalling routes promote the accumulation of GRK2, it is possible that this protein contributes to increasing the genomic instability or chemoresistance of tumour cells through its role as a regulator of the cell cycle.

  Identification of a new protein involved in the modulation of the cell cycle (Spanish)