N. Huang, F. Li, M. Zhang, H. Zhou, Z. Chen, X. Ma, L. Yang, X. Wu, J. Zhong, F. Xiao, X. Yang, K. Zhao, X. Li, X. Xia, Z. Liu, S. Gao, N. Zhang, An Upstream Open Reading Frame in Phosphatase and Tensin Homolog Encodes a Circuit Breaker of Lactate Metabolism. Cell Metab. 33, 128-144.e9 (2021).
Nu Zhang and colleagues present a tour-de-force effort to discovery, characterize and potentially therapeuterize a novel micropeptide MP31 against glioblastoma. MP31 is encoded by a uORF in PTEN and inhibits lactate dehydrogenase activity by competing with NAD+ at LDHA/B. MP31 thereby puts the brakes on lactate metabolism and holds promise for combating lactate-dependent tumors such as GBM. A true masterpiece of SEP/sORF discovery!