Homeodomain-interacting protein kinase 2 plays an important role in normal terminal erythroid differentiation.
Gene-targeting experiments report that the homeodomain-interacting protein kinases 1 and 2, Hipk1 and Hipk2, are essential but redundant in hematopoietic development because Hipk1/Hipk2 double-deficient animals exhibit severe defects in hematopoiesis and vasculogenesis, whereas the single knockouts do not. These serine-threonine kinases phosphorylate and consequently modify the functions of several important hematopoietic transcription factors and cofactors. Here we show that Hipk2 knockdown alone plays a significant role in terminal fetal liver erythroid differentiation. Hipk1 and Hipk2 are highly induced during primary mouse fetal liver erythropoiesis. Specific knockdown of Hipk2 inhibits terminal erythroid cell proliferation (explained in part by impaired cell-cycle progression as well as increased apoptosis) and terminal enucleation as well as the accumulation of hemoglobin. Hipk2 knockdown also reduces the transcription of many genes involved in proliferation and apoptosis as well as important, erythroid-specific genes involved in hemoglobin biosynthesis, such as alpha-globin and mitoferrin 1, demonstrating that Hipk2 plays an important role in some but not all aspects of normal terminal erythroid differentiation.
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Shilpa M
SM
Hattangadi
Karly A
KA
Burke
Harvey F
HF
Lodish
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D041905:Erythroid Cells / Q000201:enzymology*; D004920:Erythropoiesis / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006454:Hemoglobins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D026901:Membrane Transport Proteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; D006454:Hemoglobins; D026901:Membrane Transport Proteins; C509051:mitoferrin protein, mouse; D011494:Protein Kinases; C492003:Hipk2 protein, mouse; C115113:Hipk1 protein, mouse; D017346:Protein Serine-Threonine Kinases