期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
卷 1783, 期 2, 页码 246-252出版社
ELSEVIER
DOI: 10.1016/j.bbamcr.2007.07.010
关键词
iron; IRP2; HOIL-1; ubiquitylation; degradation; HEK293
资金
- NIDDK NIH HHS [P30 DK072437, T32DK00715, 1P30DK072437] Funding Source: Medline
- NIGMS NIH HHS [R01 GM045201-16, R01 GM045201] Funding Source: Medline
- PHS HHS [R01GMS45201] Funding Source: Medline
Iron regulatory protein 2 (IRP2) binds to iron-responsive elements (IREs) to regulate the translation and stability of mRNAs encoding several proteins involved in mammalian iron homeostasis. Increases in cellular iron stimulate the polyubiquitylation and proteasomal degradation of IRP2. One study has suggested that haem-oxidized IRP2 ubiquitin ligase-1 (HOIL-1) binds to a unique 73-amino acid (aa) domain in IRP2 in an iron-dependent manner to regulate IRP2 polyubiquitylation and degradation. Other studies have questioned the role of the 73-aa domain in iron-dependent IRP2 degradation. We investigated the potential role of HOIL-1 in the iron-mediated degradation of IRP2 in human embryonic kidney 293 (HEK293) cells. We found that transiently expressed HOIL-1 and IRP2 interact via the 73-aa domain, but this interaction is not iron-dependent, nor does it enhance the rate of IRP2 degradation by iron. In addition, stable expression of HOIL-1 does not alter the iron-dependent degradation or RNA-binding activity of endogenous IRP2. Reduction of endogenous HOIL-1 by siRNA has no affect on the iron-mediated degradation of endogenous IRP2. These data demonstrate that HOIL-1 is not required for iron-dependent degradation of IRP2 in HEK293 cells, and suggest that a HOEL-1 independent mechanism is used for IRP2 degradation in most cell types. (C) 2007 Elsevier B.V. All rights reserved.
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