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Fig. 8. Tentative model of the mechanisms that influence ErbB2 downregulation in response to geldanamycin. Geldanamycin releases ErbB2 from restraints that inhibit its mobility, leading to internalization of the receptor. These processes require proteasomal activity. Cleavage of ErbB2 is not needed for internalization of the receptor, but is a competing event. Finally, ErbB2 is degraded in lysosomes rather than in proteasomes.





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