Linked Life Data

15782113

Source:http://linkedlifedata.com/resource/pubmed/id/15782113

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
26
pubmed:dateCreated
2005-6-16
pubmed:abstractText
The mitotic spindle assembly checkpoint ensures proper chromosome segregation during mitosis by inhibiting the onset of anaphase until all kinetochores are attached to the mitotic spindle and tension across the kinetochores is generated. Here, we report that the stable partial downregulation of the spindle checkpoint gene MAD1, which is observed in human cancer, leads to a functional inactivation of the spindle checkpoint resulting in gross aneuploidy. Interestingly, although Mad1 is thought to act as a kinetochore based activator of Mad2 during checkpoint activation, we show that normal levels of Mad2, but not of Mad1, are required for preventing premature sister chromatid separation and for maintaining the timing of an undisturbed mitosis, suggesting a Mad1 independent function of Mad2 that operates independent of its checkpoint function. Most significantly, a partial repression of either MAD1 or MAD2 confers resistance to nocodazole, a drug that inhibits microtubule attachment. In contrast, sensitivity to clinically relevant drugs like taxol or monastrol that inhibit the generation of tension across kinetochores is not modulated by partial downregulation of MAD1, suggesting a functional bifurcation of spindle checkpoint dependent apoptotic pathways.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
16
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4301-10
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Partial downregulation of MAD1 causes spindle checkpoint inactivation and aneuploidy, but does not confer resistance towards taxol.
pubmed:affiliation
Institute for Molecular Biology and Tumor Research (IMT), Philipps University Marburg, Emil-Mannkopff-Strasse 2, D-35037 Marburg, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't