Naa20, also known as N-α-acetyltransferase 20, is the catalytic subunit of the NatB complex. NatB is responsible for N-terminal acetylation of approximately 20% of the human proteome, a modification crucial for protein homeostasis, localization, and interactions [2,3,4]. This process is linked to various biological processes and human diseases [3]. Genetic models, such as in yeast and mice, have been valuable for studying Naa20's functions [6,7].

In triple-negative breast cancer (TNBC), Naa20 expression is higher in cancer tissues. Knockdown of Naa20 in TNBC cells inhibits cell viability, migration, and invasion, and reduces EGFR expression. Naa20 interacts with Rab5A, and over-expression of Naa20 potentiates Rab5A expression. Knockdown of Rab5A inhibits EGFR and downstream signaling, while Naa20 over-expression offsets this effect. In vivo, Naa20 knockdown suppresses tumor growth in a xenograft mouse model [1]. In hepatocellular carcinoma (HCC), Naa20 promotes oncogenic properties by inhibiting the LKB1-AMPK-mTOR axis [5]. In NatB-deficient mouse embryonic fibroblasts (Naa20 -/-), there is reduced responsiveness to an extrinsic pro-apoptotic stimulus due to procaspase-8 degradation [7].

In conclusion, Naa20, as a key component of the NatB complex, plays significant roles in protein N-terminal acetylation, which impacts multiple biological processes. Model-based research, especially the use of KO mouse models, has revealed its importance in diseases like TNBC and HCC, highlighting its potential as a therapeutic target.

References:

1. Qiao, Lei, Dong, Chao, Jia, Wenlei, Ma, Binlin. 2023. NAA20 recruits Rin2 and promotes triple-negative breast cancer progression by regulating Rab5A-mediated activation of EGFR signaling. In Cellular signalling, 112, 110922. doi:10.1016/j.cellsig.2023.110922. https://pubmed.ncbi.nlm.nih.gov/37827343/

2. D'Onofrio, Gianluca, Cuccurullo, Claudia, Larsen, Silje Kathrine, Arnesen, Thomas, Bilo, Leonilda. 2023. Novel biallelic variants expand the phenotype of NAA20-related syndrome. In Clinical genetics, 104, 371-376. doi:10.1111/cge.14359. https://pubmed.ncbi.nlm.nih.gov/37191084/

3. Layer, Dominik, Kopp, Jürgen, Fontanillo, Miriam, Lapouge, Karine, Sinning, Irmgard. 2021. Structural basis of Naa20 activity towards a canonical NatB substrate. In Communications biology, 4, 2. doi:10.1038/s42003-020-01546-4. https://pubmed.ncbi.nlm.nih.gov/33398031/

4. Morrison, Jennifer, Altuwaijri, Norah K, Brønstad, Kirsten, Alkuraya, Fowzan S, Arnesen, Thomas. 2021. Missense NAA20 variants impairing the NatB protein N-terminal acetyltransferase cause autosomal recessive developmental delay, intellectual disability, and microcephaly. In Genetics in medicine : official journal of the American College of Medical Genetics, 23, 2213-2218. doi:10.1038/s41436-021-01264-0. https://pubmed.ncbi.nlm.nih.gov/34230638/

5. Jung, Taek-Yeol, Ryu, Jae-Eun, Jang, Mi-Mi, Ju, Bong-Gun, Kim, Hyun-Seok. 2020. Naa20, the catalytic subunit of NatB complex, contributes to hepatocellular carcinoma by regulating the LKB1-AMPK-mTOR axis. In Experimental & molecular medicine, 52, 1831-1844. doi:10.1038/s12276-020-00525-3. https://pubmed.ncbi.nlm.nih.gov/33219302/

6. Lee, Kang-Eun, Ahn, Jun-Young, Kim, Jeong-Mok, Hwang, Cheol-Sang. 2014. Synthetic lethal screen of NAA20, a catalytic subunit gene of NatB N-terminal acetylase in Saccharomyces cerevisiae. In Journal of microbiology (Seoul, Korea), 52, 842-8. doi:10.1007/s12275-014-3694-z. https://pubmed.ncbi.nlm.nih.gov/25163837/

7. Guedes, Joana P, Boyer, Jean Baptiste, Elurbide, Jasmine, Giglione, Carmela, Aldabe, Rafael. 2024. NatB Protects Procaspase-8 from UBR4-Mediated Degradation and Is Required for Full Induction of the Extrinsic Apoptosis Pathway. In Molecular and cellular biology, 44, 358-371. doi:10.1080/10985549.2024.2382453. https://pubmed.ncbi.nlm.nih.gov/39099191/