Skip to main content
Fig. 3 | Epigenetics & Chromatin

Fig. 3

From: Histone N-alpha terminal modifications: genome regulation at the tip of the tail

Fig. 3

The function of NAA40-mediated N-acH4 in gene expression and cancer. NAA40 is mainly located in the cytoplasm where it binds to ribosomes and catalyzes the co-translational Nt-acetylation of histones. Although NAA40 can be also found in the nucleus, its function there remains unknown. In the presence of high levels of NAA40, N-alpha terminal acetylation on histone H4 (N-acH4) catalyzed by NAA40 blocks CK2α-mediated phosphorylation on the side chain of serine 1 residue (H4S1ph). As a result, the expression of Slug gene is activated inducing lung cancer cell migration and metastasis [28]. Additionally, NAA40-mediated N-acH4 promotes the expression of PRMT5 enzyme which then catalyzes the addition of symmetric dimethylation on the adjacent arginine 3 residue (H4R3me2s). This activates the expression of oncogenes (e.g., FGFR3 and eIF4e) while it prevents the expression of tumour suppressor genes (TSGs) (e.g., p21 and RBL2) leading to increased CRC cell growth [30]. In the absence of NAA40 and of its corresponding N-acH4, the CK2α kinase is able to accumulate in the nucleus where it binds histone H4 and catalyzes H4S1ph leading to Slug silencing and inhibition of lung cancer cell invasion. Lack of NAA40 also suppresses PRMT5 expression and thus attenuates H4R3me2s resulting in silencing of oncogenes and reactivation of TSGs delaying CRC cell growth

Back to article page
\