ITPKA phosphorylates PYCR1 and promotes the progression of glioma

• Published in: Heliyon 2024-08, Vol.10 (15), p.e35303, Article e35303
• Main Authors: Luo, Xiangying, Chen, Tao, Deng, Junyi, Liu, Ziyuan, Bi, Changlong, Lan, Song
• Format: Article
• Language: English
• Subjects: Glioma; ITPKA; Phosphorylation; Posttranslational modification; PYCR1
• ISSN: 2405-8440; 2405-8440
• DOI: 10.1016/j.heliyon.2024.e35303

Glioma is one of the prevalent malignancies, and identifying therapeutic targets for glioma is highly important. Findings of current study revealed that inositol-trisphosphate 3-kinase A (ITPKA) was found abnormally over expressed and thereby exhibited poor prognosis with glioma. Extensive academic research has meticulously elucidated ITPKA's pivotal role in enhancing glioma cell proliferation and invasion, highlighting its significance in oncogenic pathways and cellular dynamics specific to aggressive brain tumors. Inhibiting the ITPKA has wide scope to reduce the tumorigenicity in gliomas in vivo. We also noticed that ITPKA interacts with PYCR1 and phosphorylates serine 29 of PYCR1. Phosphorylation of serine 29 inhibits the E3 ligase Stub1-mediated ubiquitination of PYCR1, thereby stabilizing its protein level. Based on our findings, it was determined that the phosphorylation of serine 29 in PYCR1 by ITPKA enhances the stability of the phosphorylated PYCR1 protein. This, in turn, involved significantly in oncogenic function of ITPKA in glioblastoma. Consequently, ITPKA holds promise as a potential target in prospective glioma therapy.