A new chemotherapeutic drug was identified that targets the TGF signaling pathwa

Question

A new chemotherapeutic drug was identified that targets the TGF signaling pathway leading to a decrease in the transcription of the gene PAI-1. Researchers trying to identify the drug’s mechanism of action performed a series of experiments with the results outlined below.

In the presence of the drug…

• ChIP immunopreciptation analysis showed that the R-Smad / Co-Smad complex never bound to the transcriptional activation site
• Immunofluorescent analysis showed that the R-smad / Co-Smad complex never enters the nucleus, however nuclear import is unaffected
• R-Smad is phosphorlated at the three C-terminal Serine residues.
• R-Smad binds Co-Smad

From these results, please give the best explanation of how the drug is affecting TGF signaling.

Explanation / Answer

The identified drug is inhibiting the entrance of R-Smad/Co-Smad complex from entering into the nucleus, thus preventing the transcription of the gene PAI-1.

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