Human Gene Set: STEGMEIER_PREMITOTIC_CELL_CYCLE_REGULATORS


Standard name STEGMEIER_PREMITOTIC_CELL_CYCLE_REGULATORS
Systematic name M9183
Brief description Pre-mitotic cell cycle regulators (CDC) identified in an shRNA screen of the ubiquitin pathway components.
Full description or abstract The spindle checkpoint prevents chromosome mis-segregation by delaying sister chromatid separation until all chromosomes have achieved bipolar attachment to the mitotic spindle. Its operation is essential for accurate chromosome segregation, whereas its dysregulation can contribute to birth defects and tumorigenesis. The target of the spindle checkpoint is the anaphase-promoting complex (APC), a ubiquitin ligase that promotes sister chromatid separation and progression to anaphase. Using a short hairpin RNA screen targeting components of the ubiquitin-proteasome pathway in human cells, we identified the deubiquitinating enzyme USP44 (ubiquitin-specific protease 44) as a critical regulator of the spindle checkpoint. USP44 is not required for the initial recognition of unattached kinetochores and the subsequent recruitment of checkpoint components. Instead, it prevents the premature activation of the APC by stabilizing the APC-inhibitory Mad2-Cdc20 complex. USP44 deubiquitinates the APC coactivator Cdc20 both in vitro and in vivo, and thereby directly counteracts the APC-driven disassembly of Mad2-Cdc20 complexes (discussed in an accompanying paper). Our findings suggest that a dynamic balance of ubiquitination by the APC and deubiquitination by USP44 contributes to the generation of the switch-like transition controlling anaphase entry, analogous to the way that phosphorylation and dephosphorylation of Cdk1 by Wee1 and Cdc25 controls entry into mitosis.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 17443180   Authors: Stegmeier F,Rape M,Draviam VM,Nalepa G,Sowa ME,Ang XL,McDonald ER 3rd,Li MZ,Hannon GJ,Sorger PK,Kirschner MW,Harper JW,Elledge SJ
Exact source Fig 1DS: CDC
Related gene sets (show 2 gene sets from the same authors)
External links
Filtered by similarity ?
Source species Homo sapiens
Contributed by Jessica Robertson (MSigDB Team)
Source platform or
identifier namespace		 Human_RefSeq
Dataset references  
Download gene set format: grp | gmt | xml | json | TSV metadata
Compute overlaps ? (show collections to investigate for overlap with this gene set)
Compendia expression profiles ? NG-CHM interactive heatmaps
(Please note that clustering takes a few seconds)
GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)

Legacy heatmaps (PNG)
GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
Advanced query Further investigate these 11 genes
Gene families ? Categorize these 11 genes by gene family
Show members (show 11 source identifiers mapped to 11 genes)
Version history 6.2: Renamed from STEGMEIER_PRE-MITOTIC_CELL_CYCLE_REGULATORS

See MSigDB license terms here. Please note that certain gene sets have special access terms.