Tankyrase 1 and Tankyrase 2 Are Essential but Redundant for Mouse Embryonic Development

被引:123
作者
Chiang, Y. Jeffrey [1 ]
Hsiao, Susan J. [3 ]
Yver, Dena [4 ]
Cushman, Samuel W. [4 ]
Tessarollo, Lino [2 ]
Smith, Susan [3 ]
Hodes, Richard J. [1 ,5 ]
机构
[1] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA
[2] NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD USA
[3] NYU, Sch Med, Skirball Inst, Kimmel Ctr Biol & Med, New York, NY USA
[4] NIDDKD, NIH, Bethesda, MD USA
[5] NIA, NIH, Bethesda, MD USA
来源
PLOS ONE | 2008年 / 3卷 / 07期
基金
美国国家卫生研究院;
关键词
D O I
10.1371/journal.pone.0002639
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Tankyrases are proteins with poly(ADP-ribose) polymerase activity. Human tankyrases post-translationally modify multiple proteins involved in processes including maintenance of telomere length, sister telomere association, and trafficking of glut4-containing vesicles. To date, however, little is known about in vivo functions for tankyrases. We recently reported that body size was significantly reduced in mice deficient for tankyrase 2, but that these mice otherwise appeared developmentally normal. In the present study, we report generation of tankyrase 1-deficient and tankyrase 1 and 2 double-deficient mice, and use of these mutant strains to systematically assess candidate functions of tankyrase 1 and tankyrase 2 in vivo. No defects were observed in development, telomere length maintenance, or cell cycle regulation in tankyrase 1 or tankyrase 2 knockout mice. In contrast to viability and normal development of mice singly deficient in either tankyrase, deficiency in both tankyrase 1 and tankyrase 2 results in embryonic lethality by day 10, indicating that there is substantial redundancy between tankyrase 1 and tankyrase 2, but that tankyrase function is essential for embryonic development.
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页数:10
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共 30 条
[1]   The structure and function of telomerase reverse transcriptase [J].
Autexier, Chantal ;
Lue, Neal F. .
ANNUAL REVIEW OF BIOCHEMISTRY, 2006, 75 :493-517
[2]   Telomere length measurement by fluorescence in situ hybridization and flow cytometry: Tips and pitfalls [J].
Baerlocher, GM ;
Mak, J ;
Tien, T ;
Lansdorp, PM .
CYTOMETRY, 2002, 47 (02) :89-99
[3]   Telomeres and telomerase: their mechanisms of action and the effects of altering their functions [J].
Blackburn, EH .
FEBS LETTERS, 2005, 579 (04) :859-862
[4]   Telomere shortening and tumor formation by mouse cells lacking telomerase RNA [J].
Blasco, MA ;
Lee, HW ;
Hande, MP ;
Samper, E ;
Lansdorp, PM ;
DePinho, RA ;
Greider, CW .
CELL, 1997, 91 (01) :25-34
[5]   Protein requirements for sister telomere association in human cells [J].
Canudas, Silvia ;
Houghtaling, Benjamin R. ;
Kim, Ju Youn ;
Dynek, Jasmin N. ;
Chang, William G. ;
Smith, Susan .
EMBO JOURNAL, 2007, 26 (23) :4867-4878
[6]  
CHANG P, 2005, NAT CELL BIOL
[7]   NuMA is a major acceptor of poly(ADP-ribosyl)ation by tankyrase 1 in mitosis [J].
Chang, W ;
Dynek, JN ;
Smith, S .
BIOCHEMICAL JOURNAL, 2005, 391 :177-184
[8]   TRF1 is degraded by ubiquitin-mediated proteolysis after release from telomeres [J].
Chang, W ;
Dynek, JN ;
Smith, S .
GENES & DEVELOPMENT, 2003, 17 (11) :1328-1333
[9]   Tankyrase is a Golgi-associated mitogen-activated protein kinase substrate that interacts with IRAP in GLUT4 vesicles [J].
Chi, NW ;
Lodish, HF .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (49) :38437-38444
[10]   Generation and characterization of telomere length maintenance in tankyrase 2-deficient mice [J].
Chiang, YJ ;
Nguyen, ML ;
Gurunathan, S ;
Kaminker, P ;
Tessarollo, L ;
Campisi, J ;
Hodes, RJ .
MOLECULAR AND CELLULAR BIOLOGY, 2006, 26 (06) :2037-2043