TRPV1 is activated by several stimuli, including the binding of capsaicin, a chemical found in chili peppers. Capsaicin enters the cell by simple diffusion and then binds to one of the transmembrane domains of TRPV1, which opens the ion channel. The opening of the TRPV1 channel allows Ca2+ ions to enter the cell, leading to the activation of the enzyme calcineurin. Calcineurin removes phosphate groups from the phosphorylated form of the transcription factor NFAT2, which is typically found in the cytoplasm. Once dephosphorylated, NFAT2 moves into the nucleus, where it blocks the transcription of another protein, AFT3. AFT3, when active, prevents the cell cycle regulatory protein pGoG from inducing apoptosis and blocking cell division.
a) Describe the characteristics of capsaicin that allow it to enter the cell before binding to a transmembrane domain of TRPV1. Describe what prevents NFAT2 from inhibiting ATF3 expression in the absence of calcineurin.
b)The pGoG protein is known to indirectly interfere with the interaction between cyclins and cyclin-dependent kinases. Explain why this prevents DNA replication from happening in the cell.
c)Researchers discover a mutation that results in the constant expression of ATF3 regardless of the presence of NFAT2. Predict the effect of this mutation on the cell cycle of cells treated with capsaicin. Provide reasoning to justify your prediction.
d)Researcher claim that capsaicin could be used as a potential treatment for melanoma, a type of skin cancer. Support the researchers' claim.