Duality of p27Kip1 function in tumorigenesis
- Peter Sicinski1,
- Sima Zacharek2, and
- Carla Kim2,3
- 1 Department of Cancer Biology, Dana-Farber Cancer Institute and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA;
- 2 Children’s Hospital Stem Cell Program and Department of Genetics, Harvard Medical School and Harvard Stem Cell Institute, Boston, Massachusetts 02115, USA
This extract was created in the absence of an abstract.
In this issue of Genes & Development, Besson et al. (2007) report phenotypic characteristics of a novel knock-in mouse strain expressing a mutant allele of the cell cycle inhibitor p27Kip1 that has both common and unique features when compared with a null allele. The new studies provide the first direct in vivo evidence that in addition to its role as a tumor suppressor, p27Kip1 also functions as an oncogene. The work also suggests that p27Kip1 oncogenic activity leads to aberrant stem and progenitor cell expansion in the lung and retina, respectively. Thus, p27Kip1’s new “dark side” may serve an oncogenic function that operates in less specialized cell types to influence tumorigenesis.
The ‘good’ side of p27Kip1 function
The progression of cells through the cell cycle is driven by enzymatic complexes composed of cyclins and their catalytic partners, cyclin-dependent kinases (CDKs) (Sherr and Roberts 1999). When p27Kip1 was originally cloned, it was thought to act as an inhibitor of cyclin–CDK complexes (Polyak et al. 1994a, b; Toyoshima and Hunter 1994). However, it soon became obvious that the picture was not so simple, as evidence for an additional function for p27Kip1 was provided by the observations that this cell cycle inhibitor also serves as an essential assembly factor for cyclin D–CDK4 and cyclin D–CDK6 complexes (LaBaer et al. 1997; Cheng et al. 1999). More recent studies revealed that p27Kip1 plays additional, cell cycle-independent roles. The full repertoire of these functions is only beginning to be appreciated (Fig. 1). So far, these novel functions include regulation of the actin cytoskeleton and cell migration through modulation of RhoA activity (McAllister et al. 2003; Besson et al. 2004; Wu et al. 2006), as well as promoting neuronal differentiation by stabilizing Neurogenin-2 protein (Nguyen et al. 2006). …
