Ranbp3, short for Ran-binding protein 3, is a key protein involved in nucleocytoplasmic transport. It functions as a cofactor in the chromosome region maintenance 1 (CRM1)-mediated nuclear export pathway and is associated with multiple biological processes such as cell proliferation, apoptosis, and signaling pathway regulation [4,5]. It binds to RanGTP and can influence the interaction between CRM1 and its nuclear protein export substrates, playing a crucial role in the selective nuclear export of certain proteins [4,5].

In colorectal cancer, targeting Ranbp3 with NU2058 increases the interaction between Ranbp3 and β-catenin, promoting the nuclear export of β-catenin, which inhibits the transcription of c-Myc and cyclin D1, leading to cell senescence and suppressing tumorigenesis [1]. In chronic myeloid leukemia, silencing Ranbp3 inhibits cell proliferation, induces apoptosis, and enhances drug sensitivity. The tumor suppressor axis (TGF-β)-SMAD2/3-p21 is related to the anti-proliferation effect, and the decrease of cytoplasmic ERK1/2 leads to increased apoptosis and enhanced chemosensitivity [2]. In melanoma, Ranbp3 is required for cell proliferation and survival. Silencing Ranbp3 reinstates the TGF-β-Smad2/3-p21(Cip1) tumor-suppressor axis, and its function is necessary for the nuclear exit of extracellular signal-regulated kinase, which is associated with apoptosis [3].

In conclusion, Ranbp3 is essential for nucleocytoplasmic transport and plays a significant role in various biological processes and diseases. Loss-of-function experiments in different cell lines as described in the references have revealed its importance in regulating cell proliferation, apoptosis, and drug sensitivity in colorectal cancer, chronic myeloid leukemia, and melanoma, providing potential therapeutic targets for these diseases.

References:

1. Zheng, Can-Can, Liao, Long, Liu, Ya-Ping, Xu, Wen Wen, Li, Bin. 2022. Blockade of Nuclear β-Catenin Signaling via Direct Targeting of RanBP3 with NU2058 Induces Cell Senescence to Suppress Colorectal Tumorigenesis. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 9, e2202528. doi:10.1002/advs.202202528. https://pubmed.ncbi.nlm.nih.gov/36270974/

2. Li, Qian, Huang, Zhenglan, Peng, Yuhang, Mou, Ke, Feng, Wenli. 2021. RanBP3 Regulates Proliferation, Apoptosis and Chemosensitivity of Chronic Myeloid Leukemia Cells via Mediating SMAD2/3 and ERK1/2 Nuclear Transport. In Frontiers in oncology, 11, 698410. doi:10.3389/fonc.2021.698410. https://pubmed.ncbi.nlm.nih.gov/34504783/

3. Pathria, Gaurav, Garg, Bhavuk, Wagner, Christine, Jalili, Ahmad, Wagner, Stephan N. . RanBP3 Regulates Melanoma Cell Proliferation via Selective Control of Nuclear Export. In The Journal of investigative dermatology, 136, 264-74. doi:10.1038/JID.2015.401. https://pubmed.ncbi.nlm.nih.gov/26763446/

4. Englmeier, L, Fornerod, M, Bischoff, F R, Mattaj, I W, Kutay, U. 2001. RanBP3 influences interactions between CRM1 and its nuclear protein export substrates. In EMBO reports, 2, 926-32. doi:. https://pubmed.ncbi.nlm.nih.gov/11571268/

5. Langer, Karla, Dian, Cyril, Rybin, Vladimir, Müller, Christoph W, Petosa, Carlo. 2011. Insights into the function of the CRM1 cofactor RanBP3 from the structure of its Ran-binding domain. In PloS one, 6, e17011. doi:10.1371/journal.pone.0017011. https://pubmed.ncbi.nlm.nih.gov/21364925/