Question

You are studying a transcriptional activator protein called CYK1, which activates cytokine genes in immune cells and has both a nuclear localization and a nuclear export signal and is normally found both in the nucleus and in the cytosol at comparable concentrations. CYK1 has a high-affinity binding partner in the nucleus (the binding partner is restricted to the nucleus). Upon activation of a certain signaling pathway, the binding protein partner is tagged for degradation. Explain the outcome of activation of the signaling pathway on cytokine gene expression and the localization of the transcriptional activator.

Answer 1

The binding partner is present only in the nucleus where it binds CYK1 and keeps it in the nucleus. If the binding partner is tagged for degradation downstream of a signalling pathway, then it gets degraded and bound CYK1 is released. This unmasks the nuclear export signal of CYK1 and CYK1 gets exported to the cytosol.

Low presence of the transcriptional activator CYK1 in the nucleus will cause reduced transcription and expression of the target cytokine genes in immune cells.

So if this particular signalling pathway is activated, it causes CYK1 to be localized more in cytosol than in nucleus; and causes reduction in the expression of the cytokine genes.