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Literature summary for 2.3.1.257 extracted from

  • Demetriadou, C.; Pavlou, D.; Mpekris, F.; Achilleos, C.; Stylianopoulos, T.; Zaravinos, A.; Papageorgis, P.; Kirmizis, A.
    NAA40 contributes to colorectal cancer growth by controlling PRMT5 expression (2019), Cell Death Dis., 10, 236 .
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
gene NAA40, quantitative real-time PCR enzyme expression analysis in colorectal cancer cells Homo sapiens

Protein Variants

Protein Variants Comment Organism
additional information enzyme silencing by lentivirus-based shRNA sequences (NAA40-KD1 and NAA40-KD2) targeting two distinct sites of NAA40 mRNA in HCT-116, HT-29, SW-480, and SW-620 cells. Depletion of NAA40 impedes cell proliferation and results in morphological alterations, such as cellular rounding. NAA40 depletion impairs CRC xenograft tumor growth Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
acetyl-CoA + N-terminal-L-seryl1-[histone H2A] Homo sapiens
-
N-terminal-Nalpha-acetyl-L-seryl1-[histone H2A] + CoA
-
?
acetyl-CoA + N-terminal-L-seryl1-[histone H4] Homo sapiens
-
N-terminal-Nalpha-acetyl-L-seryl1-[histone H4] + CoA
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens Q86UY6
-
-

Source Tissue

Source Tissue Comment Organism Textmining
colon
-
Homo sapiens
-
colorectal cancer cell CRC, NAA40 protein and mRNA levels are commonly increased in CRC primary tissues compared to non-malignant specimens. Quantitative real-time PCR enzyme expression analysis in colorectal cancer cells Homo sapiens
-
HCT-116 cell
-
Homo sapiens
-
HT-29 cell
-
Homo sapiens
-
SW-480 cell
-
Homo sapiens
-
SW-620 cell
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
acetyl-CoA + N-terminal-L-seryl1-[histone H2A]
-
Homo sapiens N-terminal-Nalpha-acetyl-L-seryl1-[histone H2A] + CoA
-
?
acetyl-CoA + N-terminal-L-seryl1-[histone H4]
-
Homo sapiens N-terminal-Nalpha-acetyl-L-seryl1-[histone H4] + CoA
-
?

Synonyms

Synonyms Comment Organism
N-acetyltransferase 11 UniProt Homo sapiens
N-alpha-acetyltransferase 40
-
Homo sapiens
Naa40
-
Homo sapiens
Nat11 UniProt Homo sapiens

Cofactor

Cofactor Comment Organism Structure
acetyl-CoA
-
Homo sapiens

Expression

Organism Comment Expression
Homo sapiens NAA40 is significantly upregulated in primary colorectal cancer (CRC) tissues and promotes CRC cell growth both in vitro and in xenograft tumor models up

General Information

General Information Comment Organism
malfunction depletion of NAA40 inhibits cell proliferation and survival of CRC cell lines and increases their sensitivity to 5-fluorouracil (5-FU) treatment. Moreover, the absence of NAA40 significantly delays the growth of human CRC xenograft tumors. NAA40 knockdown and loss of N-acH4 reduce the levels of symmetric dimethylation of histone H4 (H4R3me2s) through transcriptional downregulation of protein arginine methyltransferase 5 (PRMT5). NAA40 depletion and subsequent repression of PRMT5 results in altered expression of key oncogenes and tumor suppressor genes leading to inhibition of CRC cell growth. NAA40 mRNA levels correlate with those of PRMT5 in CRC patient tissues. H4 arginine 3 symmetric dimethylation (H4R3me2s) levels are notably decreased in the absence of NAA40 and of its mediated N-acH4 compared to the SCR and mock control cells. On the other hand, reduction of NAA40 expression does not influence the total levels of monomethylation (H4R3me1) or asymmetric dimethylation (H4R3me2a) at the third residue of histone H4. Consistently, H4R3me2s levels are reduced upon NAA40 knockdown in SW-480 and SW-620 cells, while H4R3me1 and H4R3me2a levels remain unaffected. PRMT5 upregulation restores viability in NAA40-depleted CRC cells Homo sapiens
physiological function N-alpha-acetyltransferase 40 (NAA40) catalyzes the transfer of an acetyl moiety to the alpha-amino group of serine 1 (S1) on histones H4 and H2A. NAA40 and its corresponding N-terminal acetylation of histone H4 (N-acH4) is linked to colorectal cancer (CRC). NAA40 contributes to colorectal cancer growth by controlling protein arginine methyltransferase 5 (PRMT5) expression. NAA40 stimulates PRMT5 expression in CRC cells Homo sapiens