p21(Waf1/Cip1) deficiency stimulates centriole overduplication.
Inactivation of the cyclin-dependent kinase (CDK) inhibitor p21(Waf1/Cip1) (CDKN1; hereafter p21) has previously been implicated in the induction of numerical centrosome alterations. It is unclear, however, whether p21 deficiency deregulates the centrosome duplication cycle itself or causes an accumulation of centrosomes due to cell division failure and/or polyploidization. Using a novel marker for maternal centrioles, Cep170, we show here that knock-down of p21 protein expression in murine myeloblasts can stimulate excessive centriole numbers in the presence of only one mature centriole. These results indicate that p21 deficiency can trigger a bona fide overduplication of centrioles and that aberrant centrosome numbers cannot solely be explained by polyploidization as suggested by previous studies. Our findings underscore that impaired p21 expression may function as a driving force for chromosomal instability and highlight the importance of markers for maternal centrioles such as Cep170 to elucidate the pathogenesis of numerical centriole aberrations in tumor cells.
Duensing
Anette
A
Department of Pathology, Molecular Virology Program, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Ghanem
Louis
L
Steinman
Richard A
RA
Liu
Ying
Y
Duensing
Stefan
S
D000818:Animals; D002502:Centrioles / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000172:deficiency* / Q000378:metabolism*; D042381:Granulocyte Precursor Cells / Q000166:cytology; D051379:Mice; D034741:RNA, Small Interfering / Q000378:metabolism
D050759:Cyclin-Dependent Kinase Inhibitor p21; D034741:RNA, Small Interfering