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Deregulation of Rb-E2F1 Axis Causes Chromosomal Instability by Engaging the Transactivation Function of Cdc20–Anaphase-Promoting Complex/Cyclosome

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Title Deregulation of Rb-E2F1 Axis Causes Chromosomal Instability by Engaging the Transactivation Function of Cdc20–Anaphase-Promoting Complex/Cyclosome
 
Creator Nath, Somsubhra
Chowdhury, Abhishek
Dey, Sanjib
Roychoudhury, Anirban
Ganguly, Abira
Bhattacharyya, Dibyendu
Roychoudhury, Susanta
 
Subject Cancer Biology and Inflammatory Disorder Division
 
Description The E2F family of transcription factors regulates genes involved in various aspects of the cell cycle. Beyond the well-documented role in G1/S transition, mitotic regulation by E2F has also been reported. Proper mitotic progression is monitored by the spindle assembly checkpoint (SAC). The SAC ensures bipolar separation of chromosomes and thus prevents aneuploidy. There are limited reports on the regulation of the SAC by E2F. Our previous work identified the SAC protein Cdc20 as a novel transcriptional regulator of the mitotic ubiquitin carrier protein UbcH10. However, none of the Cdc20 transcription complex proteins have any
known DNA binding domain. Here we show that an E2F1-DP1 heterodimer is involved in recruitment of the Cdc20 transcription complex to the UBCH10 promoter and in transactivation of the gene. We further show that inactivation of Rb can facilitate this transactivation process. Moreover, this E2F1-mediated regulation of UbcH10 influences mitotic progression. Deregulation of this pathway results in premature anaphase, chromosomal abnormalities, and aneuploidy. We conclude that excess E2F1 due to Rb inactivation recruits the complex of Cdc20 and the anaphase-promoting complex/cyclosome (Cdc20-APC/C) to deregulate the expression of UBCH10, leading to chromosomal instability in cancer cells.
 
Publisher American Society for Microbiology
 
Date 2015
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/2241/1/MOLECULAR_AND_CELLULAR_BIOLOGY__V._35__(_2__)s_356%2D369_;2015[102].pdf
Nath, Somsubhra and Chowdhury, Abhishek and Dey, Sanjib and Roychoudhury, Anirban and Ganguly, Abira and Bhattacharyya, Dibyendu and Roychoudhury, Susanta (2015) Deregulation of Rb-E2F1 Axis Causes Chromosomal Instability by Engaging the Transactivation Function of Cdc20–Anaphase-Promoting Complex/Cyclosome. Molecular and Cellular Biology, 35 (2). pp. 356-369.
 
Relation http://dx.doi.org/10.1128/MCB.00868-14
http://www.eprints.iicb.res.in/2241/