An abundant erythroid protein that stabilizes free α-haemoglobin

Anthony J. Kihm, Yi Kong, Wei Hong, J. Eric Russell, Susan Rouda, Kazuhiko Adachi, M. Celeste Simon, Gerd A. Blobel and Mitchell J. Weiss ()
Additional contact information
Anthony J. Kihm: The Children's Hospital of Philadelphia
Yi Kong: The Children's Hospital of Philadelphia
Wei Hong: The Children's Hospital of Philadelphia
J. Eric Russell: The Children's Hospital of Philadelphia
Susan Rouda: The Children's Hospital of Philadelphia
Kazuhiko Adachi: The Children's Hospital of Philadelphia
M. Celeste Simon: University of Pennsylvania
Gerd A. Blobel: The Children's Hospital of Philadelphia
Mitchell J. Weiss: The Children's Hospital of Philadelphia

Nature, 2002, vol. 417, issue 6890, 758-763

Abstract: Abstract The development of red blood cells (erythrocytes) is distinguished by high-level production of the oxygen carrier, haemoglobin A (HbA), a heterotetramer of α- and β-haemoglobin subunits. HbA synthesis is coordinated to minimize the accumulation of free subunits that form cytotoxic precipitates1,2,3. Molecular chaperones that regulate globin subunit stability, folding or assembly have been proposed to exist but have never been identified. Here we identify a protein stabilizing free α-haemoglobin by using a screen for genes induced by the essential erythroid transcription factor GATA-1 (refs 4, 5). Alpha Haemoglobin Stabilizing Protein (AHSP) is an abundant, erythroid-specific protein that forms a stable complex with free α-haemoglobin but not with β-haemoglobin or haemoglobin A (α2β2). Moreover, AHSP specifically protects free α-haemoglobin from precipitation in solution and in live cells. AHSP-gene-ablated mice exhibit reticulocytosis and abnormal erythrocyte morphology with intracellular inclusion bodies that stain positively for denatured haemoglobins. Hence, AHSP is required for normal erythropoiesis, probably acting to block the deleterious effects of free α-haemoglobin precipitation. Accordingly, AHSP gene dosage is predicted to modulate pathological states of α-haemoglobin excess, such as β-thalassaemia.

Date: 2002
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/nature00803 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:417:y:2002:i:6890:d:10.1038_nature00803

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature00803

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().