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Abstract:
Imbalanced chromosomal content, or aneuploidy, strongly affects the
physiology of eukaryotic cells. The consequences of these effects are
frequently detrimental, in particular in Metazoans. In humans,
aneuploidy has been causatively linked to pathological conditions such
as spontaneous abortions, trisomy syndromes and cancer. However, only in
recent years have we witnessed an unraveling of the complex phenotypes
that are caused by aneuploidy. Importantly, it has become apparent that
aneuploidy evokes global and uniform changes that cannot be explained by
the altered expression of the specific genes located on aneuploid
chromosomes. Recent discoveries show that aneuploidy negatively affects
protein folding; in particular, the functions of the molecular chaperone
Heat Shock Protein 90 (HSP90) and the upstream regulator of heat
shock-induced transcription, Heat Shock Factor 1 (HSF1), are impaired.
Here we discuss the possible causes and consequences of this impairment
and propose that the protein folding stress instigated by aneuploidy may
be a common feature of conditions as variable as cancer and trisomy
syndromes.
