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PMID:20231426

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Citation

Hattangadi, SM, Burke, KA and Lodish, HF (2010) Homeodomain-interacting protein kinase 2 plays an important role in normal terminal erythroid differentiation. Blood 115:4853-61

Abstract

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.

Links

PubMed PMC2890178 Online version:10.1182/blood-2009-07-235093

Keywords

Animals; Apoptosis/physiology; Carrier Proteins/genetics; Carrier Proteins/metabolism; Cell Cycle/physiology; Cell Differentiation/physiology; Erythroid Cells/enzymology; Erythropoiesis/physiology; Gene Knockdown Techniques; Hemoglobins/biosynthesis; Hemoglobins/genetics; Humans; Membrane Transport Proteins/biosynthesis; Membrane Transport Proteins/genetics; Mice; Protein Kinases/genetics; Protein Kinases/metabolism; Protein-Serine-Threonine Kinases/genetics; Protein-Serine-Threonine Kinases/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:HIPK1

involved_in

GO:0060216: definitive hemopoiesis

ECO:0000250: sequence similarity evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:HIPK2

involved_in

GO:0030218: erythrocyte differentiation

ECO:0000250: sequence similarity evidence used in manual assertion

P

Seeded From UniProt

Missing: with/from

See also

References

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