Research: Centro Nacional de Investigaciones Oncológicas (CNIO)Centro Nacional de Investigaciones Oncológicas · Cell Division and Cancer GroupSpain · MadridGroup Leader
Teaching: Universidad Autónoma de MadridUniversidad Autónoma de Madrid · Departamento de Biología MolecularSpain · MadridHonorary Professor
Research: Centro Nacional de Investigaciones Oncológicas (CNIO)Centro Nacional de Investigaciones Oncológicas (CNIO) · Molecular Oncology · Experimental OncologySpain · MadridMariano Barbacid's group
Research: New York University (NYU) Medical CenterNew York University Medical Center · Angel PellicerUSA · Manhattan, NYC
Research: Centrum fur Molekulare Biologie HeidelbergCentrum fur Molekulare Biologie · Hermann BujardGermany · Heidelberg
Research: Universidad de LeónUniversidad de León · Department of Ecology, Genetics and Microbiology · Juan Francisco MartínSpain · LeónPhD work
Can anyone suggest any pharmacological reagents or genetically modified cells that can prevent cell cycle arrest?
By Sureshbabu Angara · Yale UniversityVery difficult to answer that question. You can prevent cell cycle arrest upon DNA damage using UCN-01 or caffeine but these cells will continue the c... [more]Very difficult to answer that question. You can prevent cell cycle arrest upon DNA damage using UCN-01 or caffeine but these cells will continue the cell cycle WITH damage. As you want to "enhance cell proliferation (withoyt any defects)" you will need to either a) eliminate the event that is inducing the DNA damage or b) enhance DNA repair (impossible to suggest pharmacological agents for these...)Following
Answer added in Stem Cell Culture31 Cell quiescence - How do you define it?Going back to the original question. Neither quiescence (non-dividing state) nor senescence (irreversible arrest) have nothing to do with cell death. ... [more]Going back to the original question. Neither quiescence (non-dividing state) nor senescence (irreversible arrest) have nothing to do with cell death. These are independent terms. The quiescent G0 phase can be as long as the cell life span.Following
Answer added in Stem Cell Culture31 Cell quiescence - How do you define it?G1 is a phase of the cell cycle and quiescent cells are NOT in the cell cycleG1 is a phase of the cell cycle and quiescent cells are NOT in the cell cycleFollowing
Reversal of cell cycle arrest approach
By Sureshbabu Angara · Yale UniversityYou need to be more specific but if the question is how to avoid the cell cycle arrest of primary epithelial cells in culture you then need to inhibit... [more]You need to be more specific but if the question is how to avoid the cell cycle arrest of primary epithelial cells in culture you then need to inhibit pRb and/or p53 pathways (culture shock) as well as the antiproliferative consequences of telomere shortening. But the answer depends on the species, tissue, cell type, etc.Following
Cell Cycle: What direct methods are being used to measure cell cycle time, and what is a sufficient sample size?
Since you ask for direct methods I would say that live cell imaging is the only method you should use. No need for markers; just from cell division to... [more]Since you ask for direct methods I would say that live cell imaging is the only method you should use. No need for markers; just from cell division to cell division.Following
Article: Killing cells by targeting mitosis.[show abstract] [hide abstract]
ABSTRACT: Cell cycle deregulation is a common feature of human cancer. Tumor cells accumulate mutations that result in unscheduled proliferation, genomic instability and chromosomal instability. Several therapeutic strategies have been proposed for targeting the cell division cycle in cancer. Whereas inhibiting the initial phases of the cell cycle is likely to generate viable quiescent cells, targeting mitosis offers several possibilities for killing cancer cells. Microtubule poisons have proved efficacy in the clinic against a broad range of malignancies, and novel targeted strategies are now evaluating the inhibition of critical activities, such as cyclin-dependent kinase 1, Aurora or Polo kinases or spindle kinesins. Abrogation of the mitotic checkpoint or targeting the energetic or proteotoxic stress of aneuploid or chromosomally instable cells may also provide further benefits by inducing lethal levels of instability. Although cancer cells may display different responses to these treatments, recent data suggest that targeting mitotic exit by inhibiting the anaphase-promoting complex generates metaphase cells that invariably die in mitosis. As the efficacy of cell-cycle targeting approaches has been limited so far, further understanding of the molecular pathways modulating mitotic cell death will be required to move forward these new proposals to the clinic.Cell death and differentiation 03/2012; 19(3):369-77. · 8.24 Impact Factor
Article: Genetic cooperation between p21Cip1 and INK4 inhibitors in cellular senescence and tumor suppression.[show abstract] [hide abstract]
ABSTRACT: Cell-cycle inhibitors of the Cip/Kip and INK4 families are involved in cellular senescence and tumor suppression. Some of these proteins, p21(Cip1), p16(INK4a) and p15(INK4b), are coexpressed in response to antiproliferative signals such as cellular senescence resulting in cell-cycle arrest. To understand the roles of these inhibitors and their synergistic effect, we have characterized the growth properties and senescent behavior of primary cells deficient in p21(Cip1) and expressing an endogenous Cdk4(R24C) (cyclin-dependent kinase) mutant (Cdk4(R24C) knock-in cells) insensitive to INK4 proteins. Inactivation of both p21(Cip1) and INK4 pathways strongly cooperate in suppressing cellular senescence in vitro. These double mutant cells behavior as immortal cultures and display high sensitivity to cellular transformation by oncogenes. Moreover, mice double mutant in the INK4 and p21(Cip1) pathways (Cdk4(R24C); p21(Cip1)-null mice) display an increased incidence of specific sarcomas, suggesting a significant cooperation between these two families of cell-cycle inhibitors in senescence responses and tumor suppression in vivo.Oncogene 01/2008; 26(55):7665-74. · 6.37 Impact Factor
M. Malumbres09/2006: pages 139-147;
Article: Cyclin-dependent kinase 2 is dispensable for normal centrosome duplication but required for oncogene-induced centrosome overduplication.[show abstract] [hide abstract]
ABSTRACT: Cyclin-dependent kinase 2 (CDK2) has been proposed to function as a master regulator of centrosome duplication. Using mouse embryonic fibroblasts (MEFs) in which Cdk2 has been genetically deleted, we show here that CDK2 is not required for normal centrosome duplication, maturation and bipolar mitotic spindle formation. In contrast, Cdk2 deficiency completely abrogates aberrant centrosome duplication induced by a viral oncogene. Mechanistically, centrosome overduplication in MEFs wild-type for Cdk2 involves the formation of supernumerary immature centrosomes. These results indicate that normal and abnormal centrosome duplication have significantly different requirements for CDK2 activity and point to a role of CDK2 in licensing centrosomes for aberrant duplication. Furthermore, our findings suggest that CDK2 may be a suitable therapeutic target to inhibit centrosome-mediated chromosomal instability in tumor cells.Oncogene 06/2006; 25(20):2943-9. · 6.37 Impact Factor
[show abstract] [hide abstract]
ABSTRACT: Most human tumors harbor mutations that misregulate the early phases of the cell cycle. Here, we summarize genetic evidence, mostly obtained in our laboratory using strains of gene-targeted mice, that provides direct experimental support for a role of Cdk4 in tumor development. Moreover, these genetic studies challenge some well-established concepts regarding the role of Cdks during the early phases of the cell cycle. For instance, they have illustrated that Cdk4 and Cdk6 are not essential for cell division during embryonic development except in the hematopoietic system. More surprisingly, mice lacking Cdk2 survive for over 2 years without detectable abnormalities except in their germ cells, indicating that Cdk2 is essential for meiosis but dispensable for the normal mitotic cell cycle. Cdk2 is also dispensable for cell cycle inhibition and tumor suppression by the Cip/Kip inhibitors, p21(Cip1) and p27(Kip1). These observations have important implications not only to understand cell cycle regulation, but also to validate Cdks as potential targets for the development of therapeutic strategies to block proliferation of tumor cells.Cold Spring Harbor Symposia on Quantitative Biology 02/2005; 70:233-40.
Cell cycle, mitosis and microRNAs