Husaini Roslina, Ahmad Munirah, Soo-Beng Khoo Alan
Molecular Pathology Unit, Cancer Research Centre, Institute for Medical Research, Jalan Pahang, 50588 Kuala Lumpur, Malaysia.
BMC Res Notes. 2011 Dec 21;4:551. doi: 10.1186/1756-0500-4-551.
Nasopharyngeal carcinoma (NPC) is an epithelial malignancy, which commonly occurs in Southern China, Taiwan, North Africa and Southeast Asia. Nasopharyngeal carcinoma is strongly associated with Epstein-Barr virus infection. The p53 tumour suppressor protein is rarely mutated in NPC suggesting that the inactivation of p53 pathway in NPC could be due to the presence of EBV proteins. The aim of this work was to determine the effects of EBV proteins namely LMP1 and LMP2A on the expression levels of p53 protein.
In this work we found that LMP1, but not LMP2A, decreased p53 protein levels. Overexpression of LMP1 resulted in increased ubiquitination of p53 suggesting that the decreased p53 protein levels by LMP1 was due to increased degradation of the protein. The reduction of p53 protein levels was independent of the PI3K-Akt pathway.
LMP1, but not LMP2A, reduced p53 protein levels through the increase in the polyubiquitination of p53 protein and was independent of the PI3K-Akt pathway.
鼻咽癌(NPC)是一种上皮性恶性肿瘤,常见于中国南方、台湾、北非和东南亚。鼻咽癌与爱泼斯坦-巴尔病毒(EBV)感染密切相关。p53肿瘤抑制蛋白在鼻咽癌中很少发生突变,这表明鼻咽癌中p53通路的失活可能是由于EBV蛋白的存在。这项工作的目的是确定EBV蛋白LMP1和LMP2A对p53蛋白表达水平的影响。
在这项工作中,我们发现LMP1而非LMP2A降低了p53蛋白水平。LMP1的过表达导致p53泛素化增加,这表明LMP1导致p53蛋白水平降低是由于该蛋白降解增加。p53蛋白水平的降低与PI3K-Akt通路无关。
LMP1而非LMP2A通过增加p53蛋白的多聚泛素化降低了p53蛋白水平,且与PI3K-Akt通路无关。