Notch Takes a Knocking

The drug, called SAHM1, potently blocks the Notch1 transcription factor, a protein whose ability to influence gene expression makes it a key player in cell fate decisions and development. Faulty Notch signalling can cause certain cancers and Gregory Verdine and colleagues show that SAHM1 reduces leukaemia growth in a mouse model by interfering with Notch signalling.

Developing drugs that directly block transcription factors has proved challenging, as they lack suitable sites on their surface for small molecules to latch on, making it necessary to instead block their interaction with other proteins. Here, the problem is solved by using synthetic, cell-permeable, hydrocarbon-stapled peptides that disrupt a critical protein-protein interaction in the Notch transcription factor complex. The authors hope their approach may also prove applicable to other transcription factors.

CONTACT

Gregory Verdine (Harvard University, Cambridge, MA, USA)
E-mail: gregory_verdine@harvard.edu

Paramjit Arora (New York University, NY, USA) N&V author
E-mail: arora@nyu.edu

(C) Nature press release.

Message posted by: Trevor M. D'Souza