title: The role of p27(Kip1) in maintaining the levels of D-type cyclins in vivo.
abstract: This in vivo study employs p27-deficient mice to investigate the significance of p27 for the metabolism of D-type cyclins in differentiated cells. The absence of p27 results in decreased levels of cyclins D2 and/or D3 in some organs. As demonstrated on Leydig cells of testis, such dependency is only restricted to certain cell types including terminally differentiated ones, and the absence of p27 in these cells can interfere with their differentiation. The decrease of cyclin D caused by the absence of p27 equals the amount of cyclin D physically associated with p27 in non-mutant animals. The data indicate that it is the proportion of p27-associated cyclin D that determines the response to p27 deficiency. Cells in which the level of D-type cyclin is dependent on p27 do not up-regulate the activity of their CDK2 and CDK4 upon loss of p27, and these cells have a negligible amount of p27 bound to CDK2 and/or cyclin A/E under normal conditions. Together, the findings suggest the existence of a dual role for p27, one being a classical regulation of cell cycle via inhibition of cyclin-dependent kinases (CDK), and the other being participation in the establishment and/or maintenance of differentiated status that is realized in conjunction with D-type cyclins.
authors.affiliation: Center for Cell Therapy and Tissue Repair, Charles University, Prague, Czech Republic.
authors.forename: Vítezslav
authors.initials: V
authors.lastname: Bryja
authors.forename: Jirí
authors.initials: J
authors.lastname: Pacherník
authors.forename: Ludmila
authors.initials: L
authors.lastname: Faldíková
authors.forename: Pavel
authors.initials: P
authors.lastname: Krejcí
authors.forename: Robert
authors.initials: R
authors.lastname: Pogue
authors.forename: Iveta
authors.initials: I
authors.lastname: Nevrivá
authors.forename: Petr
authors.initials: P
authors.lastname: Dvorák
authors.forename: Ales
authors.initials: A
authors.lastname: Hampl
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D056741:Cyclin D; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D007985:Leydig Cells / Q000166:cytology / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000502:physiology; D014018:Tissue Distribution; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D056741:Cyclin D; D016213:Cyclins; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D013739:Testosterone; D018844:Cyclin-Dependent Kinases