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Molecular and Cellular Biology, May 1999, p. 3808-3815, Vol. 19, No. 5
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

HERF1, a Novel Hematopoiesis-Specific RING Finger Protein, Is Required for Terminal Differentiation of Erythroid Cells

Hironori Harada,1 Yuka Harada,1 Darin P. O'Brien,1 Dennis S. Rice,2 Clayton W. Naeve,3 and James R. Downing1,4,5,*

Departments of Pathology and Laboratory Medicine,1 Developmental Neurobiology,2 and Tumor Cell Biology4 and Center for Biotechnology,3 St. Jude Children's Research Hospital, and Department of Pathology, University of Tennessee College of Medicine,5 Memphis, Tennessee

Received 4 December 1998/Returned for modification 8 January 1999/Accepted 8 February 1999

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.

* Corresponding author. Mailing address: Departments of Pathology and Laboratory Medicine, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN 38105. Phone: (901) 495-2082. Fax: (901) 495-3749. E-mail: jim.downing{at}stjude.org.

Molecular and Cellular Biology, May 1999, p. 3808-3815, Vol. 19, No. 5
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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