GSBS Student Publications

Title

Loss of centrosome integrity induces p38-p53-p21-dependent G1-S arrest

UMMS Affiliation

Graduate School of Biomedical Sciences; Program in Molecular Medicine

Date

3-3-2007

Document Type

Article

Medical Subject Headings

Cell Line; Cells, Cultured; Centrosome; Cyclin A; Cyclin-Dependent Kinase 2; Cyclin-Dependent Kinase Inhibitor p21; G1 Phase; Hela Cells; Humans; S Phase; Tumor Suppressor Protein p53; p38 Mitogen-Activated Protein Kinases

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Centrosomes organize the microtubule cytoskeleton for both interphase and mitotic functions. They are implicated in cell-cycle progression but the mechanism is unknown. Here, we show that depletion of 14 out of 15 centrosome proteins arrests human diploid cells in G1 with reduced Cdk2-cyclin A activity and that expression of a centrosome-disrupting dominant-negative construct gives similar results. Cell-cycle arrest is always accompanied by defects in centrosome structure and function (for example, duplication and primary cilia assembly). The arrest occurs from within G1, excluding contributions from mitosis and cytokinesis. The arrest requires p38, p53 and p21, and is preceded by p38-dependent activation and centrosomal recruitment of p53. p53-deficient cells fail to arrest, leading to centrosome and spindle dysfunction and aneuploidy. We propose that loss of centrosome integrity activates a checkpoint that inhibits G1-S progression. This model satisfies the definition of a checkpoint in having three elements: a perturbation that is sensed, a transducer (p53) and a receiver (p21).

Rights and Permissions

Citation: Nat Cell Biol. 2007 Feb;9(2):160-70.

Related Resources

Link to article in PubMed

Journal Title

Nature cell biology

PubMed ID

17330329