title: Spindle assembly checkpoint protein Cdc20 transcriptionally activates expression of ubiquitin carrier protein UbcH10.
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 anaphase-promoting complex/cyclosome that, along with E2 ubiquitin-conjugating 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 co-regulated overexpression of both proteins contributes to chromosomal instability.
authors: Molecular and Human Genetics Division, Indian Institute of Chemical Biology, Council of Scientific and Industrial Research, Kolkata, India.
authors: Somsubhra
authors: S
authors: Nath
authors: Taraswi
authors: T
authors: Banerjee
authors: Debrup
authors: D
authors: Sen
authors: Tania
authors: T
authors: Das
authors: Susanta
authors: S
authors: Roychoudhury
mesh_terms: D064173:Anaphase-Promoting Complex-Cyclosome; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D043171:Chromosomal Instability / Q000502:physiology; D020090:Chromosome Segregation / Q000502:physiology; D002877:Chromosomes, Human / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D008938:Mitosis / Q000502:physiology; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*; D044763:Ubiquitin-Conjugating Enzymes / Q000096:biosynthesis* / Q000235:genetics; D043743:Ubiquitin-Protein Ligase Complexes / Q000235:genetics / Q000378:metabolism
chemical_list: D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins; C577488:CDC20 protein, human; C105156:UBE2C protein, human; D044763:Ubiquitin-Conjugating Enzymes; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome