Differential expression of classical nuclear transport factors during cellular proliferation and differentiation

We recently cloned six human importin α proteins that transport specific substrates in complex with importin β into the nucleus. We now compared their absolute expression levels in different human cell lines. We examined their expression regulation during human cell proliferation and differentiation by means of specific antibodies. Proliferation inhibition by starvation of HeLa and HaCaT cells led to a marked decrease in the expression of various nuclear transport factors. In contrast, re-addition of serum increased α-importin expression. We analyzed two models for cell differentiation and found differential importin regulation. Stimulation of rat pancreatic AR42J cell differentiation towards a neuroendocrine phenotype with activin A or towards an acinar phenotype with dexamethasone, caused strong upregulation of importin α3 and α4 expression. Phorbol ester-induced differentiation of human leukemia (HL60) cells towards a macrophage phenotype led to downregulation of importin α1 and α4 expression after 72 hours. Similarly, importins α1 and α4 displayed a strong downregulation when HL60 cells were directed towards a neutrophil phenotype by DMSO treatment. This study is the first to assess all the human importin α isoforms in documenting differential nuclear transport factor regulation during cell proliferation and differentiation.