The nuclear accumulation of the Fanconi anemia protein FANCE depends on FANCC

被引:21
作者
Leveille, France
Ferrer, Miriam
Medhurst, Annette L.
Laghmani, El Houari
Rooimans, Martin A.
Bier, Patrick
Steltenpool, Jurgen
Titus, Tom A.
Postiethwait, John H.
Hoatlin, Maureen E.
Joenje, Hans
De Winter, Johan P.
机构
[1] Free Univ Amsterdam, Ctr Med, Dept Clin Genet & Human Genet, NL-1081 BT Amsterdam, Netherlands
[2] Free Univ Amsterdam, Ctr Med, Dept Med Oncol, Div Gene Therapy, NL-1081 BT Amsterdam, Netherlands
[3] Univ Oregon, Inst Neurosci, Eugene, OR 97403 USA
[4] Oregon Hlth & Sci Univ, Dept Mol Med, Portland, OR 97201 USA
关键词
Fanconi anemia; nuclear accumulation; FANCC; FANCE; FANCD2; interaction;
D O I
10.1016/j.dnarep.2006.01.005
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
The Fanconi anemia (FA) protein FANCE is an essential component of the nuclear FA core complex, which is required for monoubiquitination of the downstream target FANCD2, an important step in the FA pathway of DNA cross-link repair. FANCE is predominantly localized in the nucleus and acts as a molecular bridge between the FA core complex and FANCD2, through direct binding of both FANCC and FANCD2. At present, it is poorly understood how the nuclear accumulation of FANCE is regulated and therefore we investigated the nuclear localization of this FA protein. We found that FANCE has a strong tendency to localize in the nucleus, since the addition of a nuclear export signal does not interfere with the nuclear localization of FANCE. We also demonstrate that the nuclear accumulation of FANCE does not rely solely on its nuclear localization signal motifs, but also on FANCC. The other FA proteins are not involved in the nuclear accumulation of FANCE, indicating a tight relationship between FANCC and FANCE, as suggested from their direct interaction. Finally, we show that the region of FANCE interacting with FANCC appears to be different from the region involved in binding FANCD2. This strengthens the idea that FANCE recruits FANCD2 to the core complex, without interfering with the binding of FANCC. (c) 2006 Elsevier B.V. All rights reserved.
引用
收藏
页码:556 / 565
页数:10
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