Expression of N-acetyl transferase human and human Arrest defective 1 proteins in thyroid neoplasms.
Protein acetylation is an important posttranslational modification regulating oncogenesis, apoptosis and cell cycle. NATH (N-acetyl transferase human) is overexpressed at the mRNA level in papillary thyroid carcinomas relative to non-neoplastic thyroid tissue. The NATH protein has recently been demonstrated to be the partner of hARD1 (human Arrest defective 1) and this complex acetylates the N-termini of proteins. ARD1 has also been implicated in the destabilization of the transcription factor HIF-1alpha (hypoxia inducible factor-1alpha). Using human thyroid papillary carcinoma biopsies and NATH- and hARD1-specific antibodies, we examined the levels of endogenous NATH and hARD1 proteins in 27 patients. We demonstrate that NATH protein level is upregulated in neoplastic versus non-neoplastic tissue in good accordance with our previous mRNA findings. In all tumors in which NATH was downregulated compared to non-neoplastic tissue, the hARD1 protein level was concomitantly reduced. SiRNA-mediated knockdown of NATH resulted in decreased levels of hARD1 protein. Taken together, these results suggest that NATH positively affects the level of hARD1 protein both in vivo and in cell cultures.
Arnesen
Thomas
T
Department of Surgical Sciences, University of Bergen and Haukeland University Hospital, Norway.
Gromyko
Darina
D
Horvli
Ole
O
Fluge
Øystein
Ø
Lillehaug
Johan
J
Varhaug
Jan Erik
JE
D000123:Acetyltransferases / Q000096:biosynthesis*; D002291:Carcinoma, Papillary / Q000201:enzymology*; D015536:Down-Regulation; D006367:HeLa Cells; D006801:Humans; D063209:N-Terminal Acetyltransferase A; D063213:N-Terminal Acetyltransferase E; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000201:enzymology*; D015854:Up-Regulation
C463022:NAA15 protein, human; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D000123:Acetyltransferases; D063209:N-Terminal Acetyltransferase A; C504824:NAA10 protein, human; D063213:N-Terminal Acetyltransferase E