IPO5 and Associated Diseases
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Backgrounds of IPO5
Importin-5 (IPO5) is located on 38q13.11 and has a target-controlled relationship with many downstream genes. IPO5 belongs to the karyopherin protein family and usually transports RNA or protein into the nucleus by binding to the nuclear localization signal (NLS) sequence. The protein constructed by the IPO5 gene comes from the import protein β family, which is a type of nuclear transporter, which is involved in the process of transporter protein. IPO5 has been shown to mediate the nuclear import of not only cellular proteins but also viral proteins. Crucial signaling pathways, such as the RAS pathway and viral replication processes, involve IPO5-dependent nuclear import steps. IPO5 is one of the newly discovered genes regulating tumor occurrence and development in recent years, which can serve as a cancer-promoting gene through targeted regulation of downstream genes. IPO5 is highly expressed in various malignant tumor tissues, which provides favorable conditions for the proliferation and differentiation of malignant tumor cells to some extent.
The Biological/Physiological Roles of IPO5
- IPO5-mediated Protein Nuclear Import.
IPO5 facilitates the nuclear import of ribosomal proteins in an in vitro translocation assay system. It has also been reported to translocate p35, a Cdk5 activator that plays a pivotal role in a multitude of nervous system activities ranging from neuronal differentiation to degeneration.
- Alteration of IPO5 in Cancer
Functional experiments indicated that IPO5 could promote the development of colorectal cancer (CRC). IPO5 is expected to be a promising oncologic target.
- Role of IPO5 in Virology
Influenza A must import several polymerase proteins to replicate, and IPO5 interacts with the viral protein PB1 and the heterodimer PA-PB1. IPO5 viral cargo is the Rev protein of the human immunodeficiency virus type 1 (HIV-1). IPO5 is one of the importins recruited by the high-risk human papillomavirus type 16 (HPV16). IPO5 plays a significant role in infectious diseases.
Fig.1 Illustration of IPO5 involvement in CRC. (Zhang, 2019)
IPO5 and Associated Diseases
The expression level of IPO5 is significantly correlated with tumor immune lymphocytes, immunosuppressants, immune activators, and chemokines, which indicates that IPO5 can participate in the tumor immune microenvironment and mediate tumor immune response. IPO5 overexpression may occur in bladder cancer, thyroid cancer, breast cancer, malignant melanoma, colorectal cancer, etc. Studies have confirmed that high expression of IPO5 in CRC and other malignant tumor tissues leads to abnormal regulation of target genes, which provides favorable conditions for the proliferation and differentiation of malignant tumor cells. Silence of IPO5 can effectively inhibit the malignant progression of esophageal cancer cells, suggesting that IPO5 acted as an oncogene in this cancer.
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Reference
- Zhang, W.; et al. IPO5 promotes the proliferation and tumorigenicity of colorectal cancer cells by mediating RASAL2 nuclear transportation. Journal of Experimental & Clinical Cancer Research. 2019, 38(1): 1-14.
