Fig. 4

Dual functional peptide endows DTX-P7 with significant anti-tumor effects. A Hsp90 is involved in multiple cellular signaling pathways that regulate apoptosis and cell survival, making it an important therapeutic target by modulating the maturation and stability of about 400 client proteins. B DTX-P7 specifically binds to cell surface Hsp90. For rapidly proliferating cells, DTX-P7 accelerates the degradation of Hsp90 through lysosome- and proteasome-dependent pathways, which induces unfolded protein response and subsequently promotes apoptosis. DTX promotes tubulin assembly into microtubules and inhibit their depolymerization, thus blocking cells in G2/M phase. The synergistic effect can be observed during the treatment of DTX-P7. C For dormant cells, DTX-P7 suppresses survival of quiescent/slowly proliferating cells via degradation of DYRK1A and subsequent cell cycle re-entry