Knockdown expression of Apc11 leads to cell-cycle distribution reduction in G2/M phase

被引:8
作者
Shi, Y. -J. [1 ]
Huo, K. -K. [1 ]
机构
[1] Fudan Univ, Inst Genet, Sch Life Sci, State Key Lab Genet Engn, Shanghai 200433, Peoples R China
关键词
siRNA; Anaphase-promoting complex; Cell proliferation; Cell cycle; ANAPHASE-PROMOTING COMPLEX; SPINDLE-ASSEMBLY CHECKPOINT; PROTEIN APC11; CANCER-CELLS; TARGET; DESTRUCTION; SLIPPAGE; GENES; DRUGS;
D O I
10.4238/2012.August.24.6
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
Anaphase-promoting complex/cyclosome (APC/C) is a key E3 ubiquitin ligase in cell division, which catalyses ubiquitination of cell-cycle regulators. Studying this complex could reveal important information regarding its application in cancer research and therapy. In this study, 4 synthesized small interfering RNAs (siRNAs) were transfected into HEK293T cells to suppress messenger RNA (mRNA) of Apc11; 2 of these reduced the amount of Apc11 mRNA by over 50%. Further experiments showed that rather than causing apoptosis, siRNA transfection led to cell-cycle distributions characterized by less time spent in G2/M phase and more time spent in G1 phase. This phenomenon was specifically induced by Apc11 silencing, as co-transfection of siRNA and an Apc11 plasmid could reverse this distribution bias. Our results suggested that siRNA targeted against Apc11 could hamper entry into G2/M phase. Current efforts are focused on elucidating the function and utility of the APC complex for clinical applications.
引用
收藏
页码:2814 / 2822
页数:9
相关论文
共 26 条
[1]   TRANSFORMING P21(RAS) MUTANTS AND C-ETS-2 ACTIVATE THE CYCLIN D1 PROMOTER THROUGH DISTINGUISHABLE REGIONS [J].
ALBANESE, C ;
JOHNSON, J ;
WATANABE, G ;
EKLUND, N ;
VU, D ;
ARNOLD, A ;
PESTELL, RG .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (40) :23589-23597
[2]   Tome-1, a trigger of mitotic entry, is degraded during G1 via the APC [J].
Ayad, NG ;
Rankin, S ;
Murakami, M ;
Jebanathirajah, J ;
Gygi, S ;
Kirschner, MW .
CELL, 2003, 113 (01) :101-113
[3]   The Cdc14B-Cdh1-Plk1 axis controls the G2 DNA-damage-response checkpoint [J].
Bassermann, Florian ;
Frescas, David ;
Guardavaccaro, Daniele ;
Busino, Luca ;
Peschiaroli, Angelo ;
Pagano, Michele .
CELL, 2008, 134 (02) :256-267
[4]   The spindle checkpoint, aneuploidy, and cancer [J].
Bharadwaj, R ;
Yu, HT .
ONCOGENE, 2004, 23 (11) :2016-2027
[5]   Mitotic checkpoint slippage in humans occurs via cyclin B destruction in the presence of an active checkpoint [J].
Brito, Daniela A. ;
Rieder, Conly L. .
CURRENT BIOLOGY, 2006, 16 (12) :1194-1200
[6]   The RING-H2-finger protein APC11 as a target of hydrogen peroxide [J].
Chang, TS ;
Jeong, WJ ;
Lee, DY ;
Cho, CS ;
Rhee, SG .
FREE RADICAL BIOLOGY AND MEDICINE, 2004, 37 (04) :521-530
[7]   Inhibitory Phosphorylation of Cyclin-Dependent Kinase 1 as a Compensatory Mechanism for Mitosis Exit [J].
Chow, Jeremy P. H. ;
Poon, Randy Y. C. ;
Ma, Hoi Tang .
MOLECULAR AND CELLULAR BIOLOGY, 2011, 31 (07) :1478-1491
[8]   Cancer cells display intra- and interline variation profound following prolonged exposure to antimitotic drugs [J].
Gascoigne, Karen E. ;
Taylor, Stephen S. .
CANCER CELL, 2008, 14 (02) :111-122
[9]   The RING-H2 finger protein APC11 and the E2 enzyme UBC4 are sufficient to ubiquitinate substrates of the anaphase-promoting complex [J].
Gmachl, M ;
Gieffers, C ;
Podtelejnikov, AV ;
Mann, M ;
Peters, JM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (16) :8973-8978
[10]   Cell death when the SAC is out of commission [J].
Huang, Hsiao-Chun ;
Shi, Jue ;
Orth, James D. ;
Mitchison, Timothy J. .
CELL CYCLE, 2010, 9 (11) :2049-2050