Spindle Assembly Checkpoint Protein Cdc20 Transcriptionally Activates Expression of Ubiquitin Carrier Protein UbcH10*□

Nath, Somsubhra and Banerjee, Taraswi and Sen, Debrup and Das, Tania and Roychoudhury, Susanta (2011) Spindle Assembly Checkpoint Protein Cdc20 Transcriptionally Activates Expression of Ubiquitin Carrier Protein UbcH10*□. The Journal of Biological Chemistry, 286 (18). pp. 15666-15677.

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    Abstract

    The spindle assembly checkpoint (SAC) ensures accurate segregation of chromosomes by monitoring kinetochore attachment of spindles during mitosis. Proper progression of mitosis depends on orderly ubiquitination and subsequent degradation of various mitotic inhibitors. At the molecular level, upon removal of SAC, Cdc20 activates E3 ubiquitin ligase anaphasepromoting complex/cyclosome that, along with E2 ubiquitinconjugating enzyme UbcH10, executes this function. Both Cdc20 and UbcH10 are overexpressed in many cancer types and are associated with defective SAC function leading to chromosomal instability. The precise mechanism of correlated overexpression of these two proteins remains elusive. We show that Cdc20 transcriptionally up-regulates UbcH10 expression. The WD40 domain of Cdc20 is required for this activity. Physical interaction between Cdc20 and anaphase-promoting complex/ cyclosome-CBP/p300 complex and its subsequent recruitment to the UBCH10 promoter are involved in this transactivation process. This transcriptional regulatory function of Cdc20 was observed to be cell cycle-specific. We hypothesize that this coregulated overexpression of both proteins contributes to chromosomal instability.

    Item Type: Article
    URI: http://www.eprints.iicb.res.in/id/eprint/111
    Subjects: Molecular & Human Genetics
    Divisions: Indian Institute of Chemical Biology
    Depositing User: Ms Sutapa Ganguly
    Date Deposited: 29 Sep 2011 12:49
    Last Modified: 06 Feb 2012 12:22
    Official URL: http://dx.doi.org/:10.1186/1476-4598-9-58
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