Fig 7.

Speculative model of how the fate of TRF1 depends on the method of TIN2 depletion. (A) RNAi-induced TIN2 depletion. TIN2 is not expressed and thus not available to protect TRF1 from degradation by the cytoplasmic E3 ligase Fbx4. (B) Siah2-induced TIN2 depletion. TIN2 is expressed and available in the cytoplasm to protect TRF1 from degradation by the cytoplasmic E3 ligase Fbx4. Upon transport to the nucleus, TIN2 is degraded by the nuclear E3 ligase Siah2. Once in the nucleus, TRF1 does not require TIN2 for protection from Fbx4 and thus remains on telomeres.