A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, which is required for S phase destruction of the replication factor Cdt1

被引：510

作者：

Jin, Jianping

Arias, Emily E.

Chen, Jing

Harper, J. Wade ^{[1
]}

Walter, Johannes C.

机构：

[1] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA

来源：

MOLECULAR CELL | 2006年 / 23卷 / 05期

关键词：

D O I：

10.1016/j.molcel.2006.08.010

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Cul4 E3 ubiquitin ligases contain the cullin 4 scaffold and the triple beta propeller Ddb1 adaptor protein, but few substrate receptors have been identified. Here, we identify 18 Ddb1- and Cul4-associated factors (DCAFs), including 14 containing WD40 repeats. DCAFs interact with multiple surfaces on Ddb1, and the interaction of WD40-containing DCAFs with Ddb1 requires a conserved "WDXR" motif. DCAF2/Cdt2, which is related to S. pombe Cdt2, functions in Xenopus egg extracts and human cells to destroy the replication licensing protein Cdt1 in S phase and after DNA damage. Depletion of human Cdt2 causes rereplication and checkpoint activation. In Xenopus, Cdt2 is recruited to replication forks via Cdt1 and PCNA, where Cdt1 ubiquitylation occurs. These studies uncover diverse substrate receptors for Cul4 and identify Cdt2 as a conserved component of the Cul4-Ddb1 E3 that is essential to destroy Cdt1 and ensure proper cell cycle regulation of DNA replication.

引用

收藏

页码：709 / 721

页数：13

相关论文

共 34 条

[1] PCNA functions as a molecular platform to trigger Cdt1 destruction and prevent re-replication [J].

Arias, EE ;

Walter, JC .

NATURE CELL BIOLOGY, 2006, 8 (01) :84-U33

[2] Replication-dependent destruction of Cdt1 limits DNA replication to a single round per cell cycle in Xenopus egg extracts [J].

Arias, EE ;

Walter, JC .

GENES & DEVELOPMENT, 2005, 19 (01) :114-126

[3] SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box [J].

Bai, C ;

Sen, P ;

Hofmann, K ;

Ma, L ;

Goebl, M ;

Harper, JW ;

Elledge, SJ .

CELL, 1996, 86 (02) :263-274

[4] Preventing re-replication of chromosomal DNA [J].

Blow, JJ ;

Dutta, A .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2005, 6 (06) :476-486

[5] CKN1 (MIM 216400):: mutations in Cockayne syndrome type A and a new common polymorphism [J].

Cao, HN ;

Williams, C ;

Carter, M ;

Hegele, RA .

JOURNAL OF HUMAN GENETICS, 2004, 49 (01) :61-63

[6] UV-damaged DNA-binding proteins are targets of CUL-4A-mediated ubiquitination and degradation [J].

Chen, XA ;

Zhang, Y ;

Douglas, L ;

Zhou, PB .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (51) :48175-48182

[7] CSA-dependent degradation of CSB by the ubiquitin-proteasome pathway establishes a link between complementation factors of the Cockayne syndrome [J].

Groisman, Regina ;

Kuraoka, Isao ;

Chevallier, Odile ;

gaye, No Gaye ;

Magnaldo, Thierry ;

Tanaka, Kiyoji ;

Kisselev, Alexei F. ;

Harel-Bellan, Annick ;

Nakatani, Yoshihiro .

GENES & DEVELOPMENT, 2006, 20 (11) :1429-1434

[8] Mitosis-specific phosphorylation of histone H3 initiates primarily within pericentromeric heterochromatin during G2 and spreads in an ordered fashion coincident with mitotic chromosome condensation [J].

Hendzel, MJ ;

Wei, Y ;

Mancini, MA ;

VanHooser, A ;

Ranalli, T ;

Brinkley, BR ;

BazettJones, DP ;

Allis, CD .

CHROMOSOMA, 1997, 106 (06) :348-360

[9] Radiation-mediated proteolysis of CDT1 by CUL4-ROC1 and CSN complexes constitutes a new checkpoint [J].

Higa, LAA ;

Mihaylov, IS ;

Banks, DP ;

Zheng, JY ;

Zhang, H .

NATURE CELL BIOLOGY, 2003, 5 (11) :1008-1015

[10] L2DTL/CDT2 interacts with the CUL4/DDB1 complex and PCNA and regulates CDT1 proteolysis in response to DNA damage [J].

Higa, Leigh Ann ;

Banks, Damon ;

Min Wu ;

Kobayashi, Ryuji ;

Hong Sun ;

Hui Zhang .

CELL CYCLE, 2006, 5 (15) :1675-1680

← 1 2 3 4 →