Targeted disruption of the murine homeodomain-interacting protein kinase-2 causes growth deficiency in vivo and cell cycle arrest in vitro.
The homeodomain-interacting protein kinase 2 (HIPK2) protein is a member of a recently identified family of nuclear protein kinases that are well conserved in various organisms. HIPK2 can bind to several homeotic factors and to a series of proteins involved in the regulation of cell survival and proliferation in response to morphogenetic and genotoxic signals. Here we report Hipk2-targeted disruption in mouse; Hipk2(-/-) mice are viable and fertile but significantly smaller than their wild-type littermates. This feature is present at birth and retained throughout the mouse adulthood. Mouse embryo fibroblasts from Hipk2(-/-) mice show a reduced proliferation rate, compared to the wild-type counterparts, with accumulation in the G0/G1 phase of the cell cycle and altered levels of the cell cycle regulators cyclin D and CDK6. Restoration of wild-type HIPK2 expression in Hipk2(-/-) cells rescues the normal phenotype supporting a role for HIPK2 in the regulation of cell proliferation.
Department of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA.
Francesco
F
Trapasso
Rami I
RI
Aqeilan
Rodolfo
R
Iuliano
Rosa
R
Visone
Eugenio
E
Gaudio
Laura
L
Ciuffini
Hansjuerg
H
Alder
Francesco
F
Paduano
Giovanna Maria
GM
Pierantoni
Silvia
S
Soddu
Carlo M
CM
Croce
Alfredo
A
Fusco
D000818:Animals; D049628:Body Size / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle; D049109:Cell Proliferation; D005298:Fertility / Q000235:genetics*; D005347:Fibroblasts / Q000166:cytology; D018390:Gene Targeting; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; C492003:Hipk2 protein, mouse; D017346:Protein Serine-Threonine Kinases