cIAP1 Localizes to the nuclear compartment and modulates the cell cycle.
We explored the location and function of the human cIAP1 protein, a member of the inhibitor of apoptosis protein (IAP) family. Unlike family member X-linked IAP (XIAP), which was predominantly cytoplasmic, the cIAP1 protein localized almost exclusively to nuclei in cells, as determined by immunofluorescence microscopy and subcellular fractionation methods. Interestingly, apoptotic stimuli induced nuclear export of cIAP1, which was blocked by a chemical caspase inhibitor. In dividing cells, cIAP1 was released into the cytosol early in mitosis, then reaccumulated in nuclei in late anaphase and in telophase, with the exception of a pool of cIAP1 that associated with the midbody. Survivin, another IAP family member, and cIAP1 were both localized on midbody microtubules at telophase, and also interacted with each other during mitosis. Cells stably overexpressing cIAP1 accumulated in G(2)-M phase and grew slower than control-transfected cells. These cIAP1-overexpressing cells also exhibited cytokinesis defects over 10 times more often than control cells and displayed a mitotic checkpoint abnormality with production of polyploid cells when exposed to microtubule-targeting drugs nocodazole and paclitaxel (Taxol). Our findings demonstrate a role for overexpressed cIAP1 in genetic instability, possibly by interfering with mitotic functions of Survivin. These findings may have important implications for cancers in which cIAP1 overexpression occurs.
Samuel
Temesgen
T
Burnham Institute, La Jolla, CA 92037, USA. reedoffice@burnham.org
Okada
Kazuya
K
Hyer
Marc
M
Welsh
Kate
K
Zapata
Juan M
JM
Reed
John C
JC
D017209:Apoptosis / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology*; D002455:Cell Division / Q000235:genetics; D002458:Cell Fractionation / Q000379:methods; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008938:Mitosis; D011506:Proteins / Q000502:physiology*; D012016:Reference Values; D044767:Ubiquitin-Protein Ligases
D051034:Inhibitor of Apoptosis Proteins; D011506:Proteins; C494833:BIRC2 protein, human; D044767:Ubiquitin-Protein Ligases