Blood, 15 April 2003, Vol. 101, No. 8, pp. 3288-3293
RED CELLS
UbcH5A, a member of human E2 ubiquitin-conjugating enzymes, is
closely related to SFT, a stimulator of iron transport, and is
up-regulated in hereditary hemochromatosis
Sven G. Gehrke,
Hans-Dieter Riedel,
Thomas Herrmann,
Boris Hadaschik,
Karin Bents,
Claudia Veltkamp, and
Wolfgang Stremmel
From the Department of Internal Medicine IV, University
Hospital Heidelberg, Heidelberg, Germany.
SFT, a stimulator of iron (Fe) transport, has been described
as a transmembrane protein that facilitates the uptake of ferrous and
ferric iron in mammalian cells. This study was initiated to investigate
the 5' regulatory region of SFT and its role in the etiology of
hereditary hemochromatosis. Sequence analyses of the putative 5'
regulatory region revealed that the SFT cDNA sequence corresponds to
intron 6/exon 7 of UbcH5A, a member of E2 ubiquitin-conjugating enzymes, which is involved in the iron-dependent ubiquitination of the
hypoxia-inducible factor (HIF) by the von Hippel-Lindau tumor
suppressor (pVHL) E3 ligase complex. Further mRNA expression studies
using a sequence-specific reverse transcriptase-polymerase chain reaction (RT-PCR) assay showed that UbcH5A is
significantly up-regulated in the liver of iron-overloaded patients
with hereditary hemochromatosis, as previously published for SFT.
However, in vitro studies on HepG2 cells failed to demonstrate any
significant UbcH5A regulation in response to iron loading or iron
chelation. In conclusion, in vivo mRNA expression data previously
obtained for SFT might be attributed to UbcH5A. The role of UbcH5A and the ubiquitination pathway in the etiology of hereditary
hemochromatosis remains to be elucidated further.
