Abstract:
:The karyopherin β proteins are involved in nuclear-cytoplasmic trafficking and are crucial for protein and RNA subcellular localization. We previously showed that Kpnβ1, a nuclear importin protein, is overexpressed in cervical cancer and is critical for cervical cancer cell survival and proliferation, whereas non-cancer cells are less dependent on its expression. This study aimed to identify the mechanisms by which inhibition of Kpnβ1 results in cervical cancer cell death. We show that the inhibition of Kpnβ1 results in the induction of apoptosis and a prolonged mitotic arrest, accompanied by distinct mitotic defects in cervical cancer cells but not non-cancer cells. In cervical cancer cells, Kpnβ1 downregulation results in sustained degradation of the antiapoptotic protein, Mcl-1, and elevated Noxa expression, as well as mitochondrial membrane permeabilization resulting in the release of cytochrome C and activation of associated caspases. Although p53 becomes stabilized in Kpnβ1 knockdown cervical cancer cells, apoptosis occurs in a p53-independent manner. These results demonstrate that blocking Kpnβ1 has potential as an anticancer therapeutic approach.
journal_name
Carcinogenesisjournal_title
Carcinogenesisauthors
Angus L,van der Watt PJ,Leaner VDdoi
10.1093/carcin/bgt491subject
Has Abstractpub_date
2014-05-01 00:00:00pages
1121-31issue
5eissn
0143-3334issn
1460-2180pii
bgt491journal_volume
35pub_type
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