Research press release


Nature Medicine

A mutant chaperone is a good chaperone



A Duvalたちは、ゲノムレベルで不安定なMSIから生じた新しい遺伝的変異によって、短い切断型シャペロンが生じることを発見した。シャペロンは、他のタンパク質の構造の安定性維持に重要な役割を果たす。正常なシャペロンは、がん細胞に形の整った構成成分を供給することによって心ならずもがん細胞の増殖を助けてしまうが、欠陥シャペロンを持つMSI腫瘍は、それほど増殖能が高くなく、治療にもよく反応する。

A new genetic variant in a chaperone protein that quells tumor progression and improves responses to therapy is reported in a study published online this week in Nature Medicine. While chaperone inhibitor compounds are being explored for cancer therapy, these findings present a naturally occurring inhibitor.

Microsatellite instability (MSI), a genetic condition that leads to the accumulation of genetic alterations, also characterizes a subset of colon cancers with better prognosis.

Alex Duval and colleagues found that a new genetic variant arising from genomically unstable MSI generates a truncated chaperone — proteins that are key to maintaining the structural stability of other proteins. As normal chaperones inadvertently aid tumor growth by providing cancer cells with shipshape building blocks, MSI tumors with the crippled chaperone are less aggressive in growth and respond better to therapies.

doi: 10.1038/nm.2457


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