Phức hợp khuyến khích anaphase/cyclosome (APC/C): Các chức năng phụ thuộc và không phụ thuộc vào chu kỳ tế bào

Biochemical Society Transactions - Tập 38 Số 1 - Trang 65-71 - 2010
Eusebio Manchado1, Manuel Eguren1, Marcos Malumbres1
1Cell Division and Cancer Group, CNIO (Centro Nacional de Investigaciones Oncológicas), Melchor Fernández Almagro 3, E-28029 Madrid, Spain

Tóm tắt

APC/C (phức hợp khuyến khích anaphase/cyclosome) là một E3 ubiquitin ligase có chức năng nhắm mục tiêu các cơ chất cụ thể để phân hủy bởi proteasome 26S. Hoạt động của APC/C phụ thuộc vào hai cofactor, cụ thể là Cdc20 (chu kỳ tế bào 20) và Cdh1, những thành phần này lựa chọn các mục tiêu thích hợp cho quá trình ubiquitination. Đã có rất nhiều nghiên cứu cho thấy rằng APC/C là một mục tiêu của SAC (kiểm soát lắp ráp thoi) trong quá trình phân bào và có vai trò quan trọng trong việc kiểm soát nồng độ protein của các yếu tố điều hòa chính trong phân bào và sao chép DNA. Thêm vào đó, các nghiên cứu gần đây đã gợi ý về các chức năng độc lập với chu kỳ tế bào của APC/C trong các tế bào không phân bào, đặc biệt là trong cấu trúc và chức năng thần kinh. Với những chức năng đáng chú ý của APC/C trong sự phát triển của tế bào và sinh lý thần kinh, việc điều chỉnh hoạt động của APC/C có thể đem lại những tác động tích cực trong điều trị lâm sàng.

Từ khóa


Tài liệu tham khảo

Thornton, 2006, Precise destruction: an emerging picture of the APC, Genes Dev., 20, 3069, 10.1101/gad.1478306

Peters, 2006, The anaphase promoting complex/cyclosome: a machine designed to destroy, Nat. Rev. Mol. Cell Biol., 7, 644, 10.1038/nrm1988

Fang, 1998, Direct binding of CDC20 protein family members activates the anaphase-promoting complex in mitosis and G1, Mol. Cell, 2, 163, 10.1016/S1097-2765(00)80126-4

Pfleger, 2000, The KEN box: an APC recognition signal distinct from the D box targeted by Cdh1, Genes Dev., 14, 655, 10.1101/gad.14.6.655

Littlepage, 2002, Identification of a new APC/C recognition domain, the A box, which is required for the Cdh1-dependent destruction of the kinase Aurora-A during mitotic exit, Genes Dev., 16, 2274, 10.1101/gad.1007302

Araki, 2005, A novel motif governs APC-dependent degradation of Drosophila ORC1 in vivo, Genes Dev., 19, 2458, 10.1101/gad.1361905

Musacchio, 2007, The spindle-assembly checkpoint in space and time, Nat. Rev. Mol. Cell Biol., 8, 379, 10.1038/nrm2163

Kulukian, 2009, Unattached kinetochores catalyze production of an anaphase inhibitor that requires a Mad2 template to prime Cdc20 for BubR1 binding, Dev. Cell, 16, 105, 10.1016/j.devcel.2008.11.005

Malureanu, 2009, BubR1 N terminus acts as a soluble inhibitor of cyclin B degradation by APC/C(Cdc20) in interphase, Dev. Cell, 16, 118, 10.1016/j.devcel.2008.11.004

Herzog, 2009, Structure of the anaphase-promoting complex/cyclosome interacting with a mitotic checkpoint complex, Science, 323, 1477, 10.1126/science.1163300

Pan, 2004, Spindle checkpoint regulates Cdc20p stability in Saccharomyces cerevisiae, Genes Dev., 18, 1439, 10.1101/gad.1184204

Nilsson, 2008, The APC/C maintains the spindle assembly checkpoint by targeting Cdc20 for destruction, Nat. Cell Biol., 10, 1411, 10.1038/ncb1799

Ge, 2009, APC/C- and Mad2-mediated degradation of Cdc20 during spindle checkpoint activation, Cell Cycle, 8, 167, 10.4161/cc.8.1.7606

Reddy, 2007, Ubiquitination by the anaphase-promoting complex drives spindle checkpoint inactivation, Nature, 446, 921, 10.1038/nature05734

Stegmeier, 2007, Anaphase initiation is regulated by antagonistic ubiquitination and deubiquitination activities, Nature, 446, 876, 10.1038/nature05694

Lim, 1998, Cdc20 is essential for the cyclosome-mediated proteolysis of both Pds1 and Clb2 during M phase in budding yeast, Curr. Biol., 8, 231, 10.1016/S0960-9822(98)70088-0

Shirayama, 1999, APC(Cdc20) promotes exit from mitosis by destroying the anaphase inhibitor Pds1 and cyclin Clb5, Nature, 402, 203, 10.1038/46080

Stemmann, 2001, Dual inhibition of sister chromatid separation at metaphase, Cell, 107, 715, 10.1016/S0092-8674(01)00603-1

Sullivan, 2007, Finishing mitosis, one step at a time, Nat. Rev. Mol. Cell Biol., 8, 894, 10.1038/nrm2276

Queralt, 2008, Cdk-counteracting phosphatases unlock mitotic exit, Curr. Opin. Cell Biol., 20, 661, 10.1016/j.ceb.2008.09.003

Geley, 2001, Anaphase-promoting complex/cyclosome-dependent proteolysis of human cyclin A starts at the beginning of mitosis and is not subject to the spindle assembly checkpoint, J. Cell Biol., 153, 137, 10.1083/jcb.153.1.137

Hames, 2001, APC/C-mediated destruction of the centrosomal kinase Nek2A occurs in early mitosis and depends upon a cyclin A-type D-box, EMBO J., 20, 7117, 10.1093/emboj/20.24.7117

Amador, 2007, APC/C(Cdc20) controls the ubiquitin-mediated degradation of p21 in prometaphase, Mol. Cell, 27, 462, 10.1016/j.molcel.2007.06.013

Wolthuis, 2008, Cdc20 and Cks direct the spindle checkpoint-independent destruction of cyclin A, Mol. Cell, 30, 290, 10.1016/j.molcel.2008.02.027

Reimann, 2001, Emi1 is a mitotic regulator that interacts with Cdc20 and inhibits the anaphase promoting complex, Cell, 105, 645, 10.1016/S0092-8674(01)00361-0

Benmaamar, 2005, Involvement of the SCF complex in the control of Cdh1 degradation in S-phase, Cell Cycle, 4, 1230, 10.4161/cc.4.9.2048

Garcia-Higuera, 2008, Genomic stability and tumour suppression by the APC/C cofactor Cdh1, Nat. Cell Biol., 10, 802, 10.1038/ncb1742

Li, 2008, The adaptor protein of the anaphase promoting complex Cdh1 is essential in maintaining replicative lifespan and in learning and memory, Nat. Cell Biol., 10, 1083, 10.1038/ncb1768

Sigrist, 1997, Drosophila fizzy-related down-regulates mitotic cyclins and is required for cell proliferation arrest and entry into endocycles, Cell, 90, 671, 10.1016/S0092-8674(00)80528-0

Gieffers, 1999, Expression of the CDH1-associated form of the anaphase-promoting complex in postmitotic neurons, Proc. Natl. Acad. Sci. U.S.A., 96, 11317, 10.1073/pnas.96.20.11317

Juo, 2004, The anaphase-promoting complex regulates the abundance of GLR-1 glutamate receptors in the ventral nerve cord of C. elegans, Curr. Biol., 14, 2057, 10.1016/j.cub.2004.11.010

van Roessel, 2004, Independent regulation of synaptic size and activity by the anaphase-promoting complex, Cell, 119, 707, 10.1016/j.cell.2004.11.028

Stegmuller, 2006, Cell-intrinsic regulation of axonal morphogenesis by the Cdh1–APC target SnoN, Neuron, 50, 389, 10.1016/j.neuron.2006.03.034

Konishi, 2004, Cdh1–APC controls axonal growth and patterning in the mammalian brain, Science, 303, 1026, 10.1126/science.1093712

Lasorella, 2006, Degradation of Id2 by the anaphase-promoting complex couples cell cycle exit and axonal growth, Nature, 442, 471, 10.1038/nature04895

Almeida, 2005, Cdh1/Hct1–APC is essential for the survival of postmitotic neurons, J. Neurosci., 25, 8115, 10.1523/JNEUROSCI.1143-05.2005

Liu, 2001, Neuronal apoptosis at the G1/S cell cycle checkpoint, Cell Tissue Res., 305, 217, 10.1007/s004410100396

Herrero-Mendez, 2009, The bioenergetic and antioxidant status of neurons is controlled by continuous degradation of a key glycolytic enzyme by APC/C-Cdh1, Nat. Cell Biol., 11, 747, 10.1038/ncb1881

Kim, 2009, A centrosomal Cdc20–APC pathway controls dendrite morphogenesis in postmitotic neurons, Cell, 136, 322, 10.1016/j.cell.2008.11.050

Carter, 2006, A signature of chromosomal instability inferred from gene expression profiles predicts clinical outcome in multiple human cancers, Nat. Genet., 38, 1043, 10.1038/ng1861

Perez de Castro, 2007, A census of mitotic cancer genes: new insights into tumor cell biology and cancer therapy, Carcinogenesis, 28, 899, 10.1093/carcin/bgm019

Singhal, 2003, Alterations in cell cycle genes in early stage lung adenocarcinoma identified by expression profiling, Cancer Biol. Ther., 2, 291, 10.4161/cbt.2.3.399

Kidokoro, 2008, CDC20, a potential cancer therapeutic target, is negatively regulated by p53, Oncogene, 27, 1562, 10.1038/sj.onc.1210799

Taniguchi, 2008, Targeting of CDC20 via small interfering RNA causes enhancement of the cytotoxicity of chemoradiation, Anticancer Res., 28, 1559

Li, 2007, Loss of Cdc20 causes a securin-dependent metaphase arrest in two-cell mouse embryos, Mol. Cell. Biol., 27, 3481, 10.1128/MCB.02088-06

Andrews, 2005, Evidence that the yeast spindle assembly checkpoint has a target other than the anaphase promoting complex, Cell Cycle, 4, 1555, 10.4161/cc.4.11.2144

Baumgarten, 2009, Strong inducible knockdown of APC/CCdc20 does not cause mitotic arrest in human somatic cells, Cell Cycle, 8, 643, 10.4161/cc.8.4.7810

Clarke, 2009, Strong inducible knockdown of Cdc20 does not cause mitotic arrest in human somatic cells: implications for cancer therapy?, Cell Cycle, 8, 515, 10.4161/cc.8.4.8057

Perez de Castro, 2008, Emerging cancer therapeutic opportunities by inhibiting mitotic kinases, Curr. Opin. Pharmacol., 8, 375, 10.1016/j.coph.2008.06.013

Luo, 2009, A genome-wide RNAi screen identifies multiple synthetic lethal interactions with the Ras oncogene, Cell, 137, 835, 10.1016/j.cell.2009.05.006