We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Vaccinia-related kinase 2 variants differentially affect breast cancer growth by regulating kinase activity.
- Authors
SEUNG-HEE GWAK; JUHYUN LEE; EUNJI OH; DOHYUN LEE; WONSHIK HAN; JONGMIN KIM; KYONG-TAI KIM
- Abstract
Genetic information is transcribed from genomic DNA to mRNA, which is then translated into threedimensional proteins. mRNAs can undergo various post-transcriptional modifications, including RNA editing that alters mRNA sequences, ultimately affecting protein function. In this study, RNA editing was identified at the 499th base (c.499) of human vaccinia-related kinase 2 (VRK2). This RNA editing changes the amino acid in the catalytic domain of VRK2 from isoleucine (with adenine base) to valine (with guanine base). Isoleucine-containing VRK2 has higher kinase activity than the valine-containing VRK2, which leads to an increase in tumor cell proliferation. Earlier we reported that VRK2 directly interacts with dystrobrevin-binding protein (dysbindin) and results in reducing its stability. Herein, we demonstrate that isoleucine-containing VRK2 decreases the level of dysbindin than valinecontaining VRK2. Dysbindin interacts with cyclin D and thereby regulates its expression and function. The reduction in the level of dysbindin by isoleucine-containing VRK2 further enhances the cyclin D expression, resulting in increased tumor growth and reduction in survival rates. It has also been observed that in patient samples, VRK2 level was elevated in breast cancer tissue compared to normal breast tissue. Additionally, the isoleucine form of VRK2 exhibited a greater increase in breast cancer tissue. Therefore, it is concluded that VRK2, especially dependent on the 167th variant amino acid, can be one of the indexes of tumor progression and proliferation.
- Subjects
TUMOR growth; BREAST cancer; RNA editing; CATALYTIC domains; AMINO acids
- Publication
Oncology Research, 2024, Vol 32, Issue 2, p421
- ISSN
0965-0407
- Publication type
Article
- DOI
10.32604/or.2023.031031