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Cancer-associated missense mutations enhance the pluripotency reprogramming activity of OCT4 and SOX17

ABSTRACT: The functional consequences of cancer-associated missense mutations are unclear for majority of proteins, here we interrogated cancer mutation databases and identified recurrently mutated positions at structural contact interface of DNA-binding domains of SOX and POU family transcription factors. We used conversion of mouse embryonic fibroblasts (MEFs) to induced pluripotent stem cells (iPSCs) as a functional read out. In this study we identified several gain-of-function mutations that enhance cellular pluripotency reprogramming by SOX2 and OCT4. Wild type SOX17 does not support pluripotency reprogramming while recurrent missense mutation SOX17-V118M converts SOX17 into a pluripotency inducer, viability of cancer cells and provides protein stability. Here, we conclude that mutational profile of SOX and OCT family factors in cancer association can give direction to design high-performance reprogramming factors.

ORGANISM(S): Mus musculus

PROVIDER: GSE134930 | GEO | 2019/10/23

REPOSITORIES: GEO

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Cancer-associated missense mutations enhance the pluripotency reprogramming activity of OCT4 and SOX17

Project description:Cancer-associated missense mutations enhance the pluripotency reprogramming activity of OCT4 and SOX17

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2014-06-24 | E-GEOD-57892 | biostudies-arrayexpress

Expression data from MCF-7 Human Breast Cancer Cells

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Effects of the expression of M1775R and A1789T BRCA1 missense variants on the transcriptome of HeLa cells

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