KPNB1 and Associated Diseases

Karyopherin subunit β1 (Kpnβ1), encoded by the KPNB1 gene, is a nuclear transporter that plays a key role in nuclear import. As an important regulator of mitosis, Kpnβ1 is involved in the regulation of cell proliferation. Studies have shown that Kpnβ1 is significantly upregulated in various cancers. Therefore, the KPNB1 gene is a potential targeting gene therapy. In the field of research related to gene therapy, Creative Biolabs is an international leading partner. From initial idea to project development, we have been helping biotechnology scientists and engineers around the world discover targeted drugs at the genetic level.

Important Function of KPNB1

The KPNB1 gene is located on human chromosome 17 (17q21) and contains 23 exons. Kpnβ1, encoded by the KPNB1 gene, is also known as importin β and belongs to the nuclear transport protein β family. Kpnβ1 is a subunit of the major nuclear receptor protein in cells. Thus, Kpnβ1 plays an integral role in the transport of transcription, signal transduction, and proliferation-related cytoplasmic molecules, including proteins, RNA, and ribosomes, to the nucleus. Kpnβ1 can combine with karyopherin subunit α1 (Kpnα1) to anchor target molecules waiting to enter the nucleus at nuclear pores. After the target molecule is transported into the nucleus, Kpnβ1 binds to uridine triphosphatase resulting in its own dissociation. Free Kpnβ1 can combine with RanGTP and return to the cytoplasm to wait for the next round of nuclear transport of target molecules. Kpnβ1 plays an important role in cell cycle regulation because Kpnβ1 is involved in a variety of cytoplasm-to-nucleus translocations closely related to cell processes.

Model for nuclear import of exogenous FGF1. Fig.1 Model for nuclear import of exogenous FGF1. (Zhen, 2012)

KPNB1-related Diseases

Disorders of cytoplasmic-nuclear transport contribute to many diseases, including cancer. It has been found that Kpnβ1 is significantly upregulated in cancers such as human glioma, gastric cancer, breast cancer, liver cancer, cervical cancer, ovarian cancer, and non-small cell lung cancer. And Kpnβ1 is associated with poor prognosis of these cancer patients. However, the mechanism of Kpnβ1-mediated nuclear import and its relationship with tumor development have not been fully elucidated. Excitingly, Kpnβ1 inhibitors targeting cancer cells were found to promote cancer cell apoptosis. In addition, during the process of the body being infected by the virus, Kpnβ1 can promote the entry of viral proteins into the nucleus, thereby promoting the proliferation of the virus. Kpnβ1 inhibitors are also currently being used in the development of antiviral drugs.

Kpnβ1 is highly expressed in NSCLC. Fig.2 Kpnβ1 is highly expressed in NSCLC. (Wang, 2018)

The KPNB1 gene plays a vital role in maintaining the basic life activities of cells. Dysregulation of the KPNB1 gene is closely related to tumor development and viral infection. In the future, the KPNB1 gene is a promising therapeutic target. The precisely targeted therapy of the KPNB1 gene is expected to be applied to the treatment of tumors. Creative Biolabs provides a one-stop technology platform for gene therapy. Please contact us with questions about your ideas to help you move forward with your project.

References

  1. Zhen, Y.; et al. Nuclear import of exogenous FGF1 requires the ER-protein LRRC59 and the importins Kpnα1 and Kpnβ1. Traffic. 2012, 13(5):650-664.
  2. Wang, H.; et al. High Kpnβ1 expression promotes non-small cell lung cancer proliferation and chemoresistance via the PI3-kinase/AKT pathway. Tissue Cell. 2018, 51:39-48.
For research use only. Not intended for any clinical use.