Document Detail

Overlapping roles for homeodomain-interacting protein kinases hipk1 and hipk2 in the mediation of cell growth in response to morphogenetic and genotoxic signals.
MedLine Citation:
PMID:  16537918     Owner:  NLM     Status:  MEDLINE    
Homeodomain-interacting protein kinase 1 (Hipk1), 2, and 3 genes encode evolutionarily conserved nuclear serine/threonine kinases, which were originally identified as interacting with homeodomain-containing proteins. Hipks have been repeatedly identified as interactors for a vast range of functional proteins, including not only transcriptional regulators and chromatin modifiers but also cytoplasmic signal transducers, transmembrane proteins, and the E2 component of SUMO ligase. Gain-of-function experiments using cultured cells indicate growth regulatory roles for Hipks on receipt of morphogenetic and genotoxic signals. However, Hipk1 and Hipk2 singly deficient mice were grossly normal, and this is expected to be due to a functional redundancy between Hipk1 and Hipk2. Therefore, we addressed the physiological roles of Hipk family proteins by using Hipk1 Hipk2 double mutants. Hipk1 Hipk2 double homozygotes are progressively lost between 9.5 and 12.5 days postcoitus and frequently fail to close the anterior neuropore and exhibit exencephaly. This is most likely due to defective proliferation in the neural fold and underlying paraxial mesoderm, particularly in the ventral region, which may be attributed to decreased responsiveness to Sonic hedgehog signals. The present study indicated the overlapping roles for Hipk1 and Hipk2 in mediating cell proliferation and apoptosis in response to morphogenetic and genotoxic signals during mouse development.
Kyoichi Isono; Kazumi Nemoto; Yuanyuan Li; Yuki Takada; Rie Suzuki; Motoya Katsuki; Akira Nakagawara; Haruhiko Koseki
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular and cellular biology     Volume:  26     ISSN:  0270-7306     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  2006 Apr 
Date Detail:
Created Date:  2006-03-15     Completed Date:  2006-04-24     Revised Date:  2014-11-17    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2758-71     Citation Subset:  IM    
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MeSH Terms
Carrier Proteins / genetics,  metabolism*
Cell Cycle
Cell Growth Processes / drug effects
Cell Proliferation
Cells, Cultured
Embryo Loss / metabolism,  pathology
Embryonic Development / genetics
Gene Expression Regulation, Developmental
Hedgehog Proteins
Homeodomain Proteins / genetics,  metabolism*
Mesoderm / cytology
Morphogenesis* / drug effects
Mutagens / metabolism*,  pharmacology
Neural Tube Defects / pathology
Neurons / cytology
Paired Box Transcription Factors / metabolism
Protein Binding
Protein Kinases / deficiency,  genetics,  metabolism*
Protein Transport
Protein-Serine-Threonine Kinases / deficiency,  genetics,  metabolism*
Signal Transduction / drug effects
Trans-Activators / metabolism
Tumor Suppressor Protein p53 / metabolism
Reg. No./Substance:
0/Carrier Proteins; 0/Hedgehog Proteins; 0/Homeodomain Proteins; 0/Mutagens; 0/Paired Box Transcription Factors; 0/Trans-Activators; 0/Tumor Suppressor Protein p53; 142661-96-9/PAX1 transcription factor; EC 2.7.-/Protein Kinases; EC 2.7.1.-/Hipk1 protein, mouse; EC 2.7.1.-/Hipk2 protein, mouse; EC Kinases
Erratum In:
Mol Cell Biol. 2014 Jul;34(14):2772

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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