Functional differences between Hsp105/110 family proteins in cell proliferation, cell division, and drug sensitivity

The mammalian HSP105/110 family consists of four members, including Hsp105 and Apg‐1, which function as molecular chaperones. Recently, we reported that Hsp105 knockdown increases sensitivity to the DNA‐damaging agent Adriamycin but decreases sensitivity to the microtubule‐targeting agent paclitaxel. However, whether the other Hsp105/110 family proteins have the same functional property is unknown. Here, we show that Apg‐1 has different roles from Hsp105 in cell proliferation, cell division, and drug sensitivity. We generated the Apg‐1‐knockdown HeLa S3 cells by lentiviral expression of Apg‐1‐targeting short hairpin RNA. Knockdown of Apg‐1 but not Hsp105 decreased cell proliferation. Apg‐1 knockdown increased cell death upon Adriamycin treatment without affecting paclitaxel sensitivity. The cell synchronization experiment suggests that Apg‐1 functions in mitotic progression at a different mitotic subphase from Hsp105, which cause difference in paclitaxel sensitivity. Since Apg‐1 is overexpressed in certain types of tumors, Apg‐1 may become a potential therapeutic target for cancer treatment without causing resistance to the microtubule‐targeting agents. In this study, we show that Apg‐1 has different roles from Hsp105 in cell proliferation, cell division, and drug sensitivity