HERF1, a novel hematopoiesis-specific RING finger protein, is required for terminal differentiation of erythroid cells.
The AML1/core binding factor beta (CBFbeta) transcription factor is essential for definitive hematopoiesis; however, the downstream pathways through which it functions remain incompletely defined. Using a differential cloning approach to define components of this pathway, we have identified a novel gene designated HERF1 (for hematopoietic RING finger 1), whose expression during development is dependent on the presence of functional AML1/CBFbeta. HERF1 contains a tripartite RING finger-B box-alpha-helical coiled-coil domain and a C-terminal region homologous to the ret proto-oncogene-encoded finger protein. Expression of HERF1 during embryogenesis coincides with the appearance of definitive erythropoiesis and in adult mice is restricted to erythroid cells, increasing 30-fold during terminal differentiation. Importantly, inhibition of HERF1 expression blocked terminal erythroid differentiation of the murine erythroleukemia cell line MEL, whereas its overexpression induced erythroid maturation. These results suggest an important role for this protein in erythropoiesis.
Harada
H
H
Departments of Pathology and Laboratory Medicine, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Harada
Y
Y
O'Brien
D P
DP
Rice
D S
DS
Naeve
C W
CW
Downing
J R
JR
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D003001:Cloning, Molecular; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D004121:Dimethyl Sulfoxide; D004920:Erythropoiesis / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000235:genetics; D013752:Tetracycline / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics; D000070584:Tripartite Motif Proteins; D016335:Zinc Fingers / Q000235:genetics*
D002352:Carrier Proteins; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C493726:Runx1 protein, mouse; C532481:TRIM10 protein, mouse; D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; D013752:Tetracycline; D004121:Dimethyl Sulfoxide