A new chemotherapeutic drug was identified that targets the TGF beta signaling p

Question

A new chemotherapeutic drug was identified that targets the TGF beta signaling pathway leading to a decrease in the transcription of the gene PAl-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 TGFbeta signaling.

Explanation / Answer

In TGF-beta signalling, only phosphorylated R-Smad binds to co- Smad. After binding this complex enters the nucleus and acts as a transcription factor.

Here, the complex has been formed and the nuclear import is also unaffected. But the complex is unable to enter the nucleus. This means that there is change in the signal present on the protein, which targets this protein complex to the nucleus.

So, the drug changes or cleaves the nuclear localisation signal present on the complex.....

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