1445-Conserved Role of Atx2 in JNK Pathway Activation

This research identifies Ataxin-2 (Atx2) as a vital, evolutionarily conserved regulator of the JNK signaling pathway, which controls processes like cell death, movement, and tumor progression. By studying Drosophila and human HeLa cells, scientists discovered that Atx2 enhances JNK activity by binding to and stabilizing hipk mRNA, an upstream component of the pathway. The study demonstrates that reducing Atx2 levels can suppress tumor growth and invasive migration, while its presence is necessary for proper physical development, such as thorax closure. Notably, this regulatory function is preserved in the human protein ATXN2L, but it is compromised when the protein undergoes polyglutamine expansion associated with neurodegenerative diseases. Ultimately, these findings position Atx2 family proteins as significant post-transcriptional controllers of cellular stress responses and potential therapeutic targets for cancer and developmental disorders.

References:

• Li X, Zhu X, Li W, et al. Conserved role of Atx2 in JNK pathway activation[J]. Cell Death & Disease, 2026.