Homeodomain-interacting protein kinases, a novel family of co-repressors for homeodomain transcription factors.
A novel family of cofactors that differentially interact with homeoproteins have been identified via a yeast two-hybrid screen. The proteins contain a conserved protein kinase domain that is separated from a domain that interacts with homeoproteins and hence are termed homeodomain-interacting protein kinases (HIPKs): HIPK1, HIPK2, and HIPK3. We show that HIPKs are nuclear kinases using GFP-HIPK fusion constructs. The DNA binding activity of the NK-3 homeoprotein is greatly enhanced by HIPK2, but this effect is independent of its phosphorylation by HIPK2. In cultured cells, HIPKs localize to nuclear speckles and potentiate the repressor activities of NK homeoproteins. The co-repressor activity of HIPKs depends on both its homeodomain interaction domain and a co-repressor domain that maps to the N terminus. Thus, HIPKs represent a heretofore undescribed family of co-repressors for homeodomain transcription factors.
Kim
Y H
YH
Laboratory of Molecular Cardiology, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA. yongsok@helix.nih.gov
Choi
C Y
CY
Lee
S J
SJ
Conti
M A
MA
Kim
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry*; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000502:physiology; D005455:Fluorescent Antibody Technique; D018398:Homeodomain Proteins / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry; D010766:Phosphorylation; D011494:Protein Kinases / Q000737:chemistry*; D017346:Protein Serine-Threonine Kinases; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000502:physiology*; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000502:physiology*
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D011494:Protein Kinases; C492003:Hipk2 protein, mouse; C109102:HIPK3 protein, human; C115113:Hipk1 protein, mouse; D017346:Protein Serine-Threonine Kinases