Dual function driver

A study led by Ludwig Oxford’s Colin Goding published in Genes and Development in November described how a transcriptional regulator called TBX2 plays a crucial role in senescence, a state of stable cell cycle arrest that can halt cancer initiation. TBX2 is a DNA-binding transcription factor—a regulator of gene expression—previously linked to transcriptional repression in embryonic development and senescence bypass and proliferation in cancer. But how it exerts its effects was unclear. Colin and his team found that TBX2 acts downstream of PI3K signaling, which is important for senescence bypass in melanomas driven by a mutated BRAF gene. In BRAF-mutated melanoma, TBX2 binds and is required for expression of E2F1, a key anti-senescence cell cycle regulator. The study vastly expands knowledge of the repertoire of genes bound and regulated by TBX2. It also provides a fundamentally different perspective on TBX2 function in senescence and development: rather than acting as a dedicated transcriptional repressor, it can also activate genes—repressing genes that block the cell cycle but maintaining expression of genes that promote cell cycle progression. TBX2 is thus a crucial regulator of cancer initiation and progression.


This article appeared in the May 2022 issue of Ludwig Link. Click here to download a copy (PDF, 2MB).


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