Arnesen Thomas, Gromyko Darina, Horvli Ole, Fluge Øystein, Lillehaug Johan, Varhaug Jan Erik
Department of Surgical Sciences, University of Bergen and Haukeland University Hospital, Norway.
Thyroid. 2005 Oct;15(10):1131-6. doi: 10.1089/thy.2005.15.1131.
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.
蛋白质乙酰化是一种重要的翻译后修饰，可调节肿瘤发生、细胞凋亡和细胞周期。相对于非肿瘤性甲状腺组织，NATH（人N - 乙酰转移酶）在甲状腺乳头状癌的mRNA水平上过度表达。最近已证明NATH蛋白是hARD1（人 Arrest defective 1）的伴侣，并且这种复合物可使蛋白质的N末端乙酰化。ARD1也与转录因子HIF - 1α（缺氧诱导因子 - 1α）的稳定性破坏有关。我们使用人甲状腺乳头状癌活检组织以及NATH和hARD1特异性抗体，检测了27例患者体内内源性NATH和hARD1蛋白的水平。我们证明，与我们之前的mRNA研究结果高度一致，肿瘤组织中NATH蛋白水平相对于非肿瘤组织上调。在所有与非肿瘤组织相比NATH下调的肿瘤中，hARD1蛋白水平也随之降低。RNA干扰介导的NATH敲低导致hARD1蛋白水平下降。综上所述，这些结果表明NATH在体内和细胞培养中均对hARD1蛋白水平产生正向影响。
