Masson Murielle, Hindelang Colette, Sibler Annie-Paule, Schwalbach Georges, Travé Gilles, Weiss Etienne
UMR 7100, Ecole Supérieure de Biotechnologie de Strasbourg, Boulevard Sébastien Brant, BP 10413, 67412 Illkirch cedex, France.
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Service de Microscopie Electronique, 1 rue Laurent Fries, 67400 Illkirch cedex, France.
J Gen Virol. 2003 Aug;84(Pt 8):2099-2104. doi: 10.1099/vir.0.18961-0.
The E6 protein of the high-risk human papillomavirus type 16 (HPV-16) is involved in the tumorigenesis of human cervical cells by targeting numerous cellular proteins. We characterized new anti-E6 monoclonal antibodies and used them for precise localization of the E6 oncoprotein within carcinoma cells. Overexpressed E6 protein was predominantly detected in the nucleus of transiently transfected HaCaT cells. While mostly localized at the periphery of condensed chromatin, E6 was also associated with nuclear ribonucleoproteic ultrastructures and with some ribosomal areas in the cytoplasm of SiHa and CaSki cells. The chimeric beta-galactosidase-E6 protein expressed in transfected HeLa cells was essentially localized in the nuclear compartment. Together, these data indicate that the E6 sequence of HPV-16 may encode a nuclear localization signal. The preferential nuclear distribution of this viral oncoprotein in HPV-transformed cells correlates with its activities at the transcriptional level.
高危型人乳头瘤病毒16型(HPV-16)的E6蛋白通过靶向多种细胞蛋白参与人宫颈细胞的肿瘤发生。我们鉴定了新的抗E6单克隆抗体,并将其用于E6癌蛋白在癌细胞内的精确定位。在瞬时转染的HaCaT细胞的细胞核中主要检测到过表达的E6蛋白。虽然E6大多定位于浓缩染色质的周边,但在SiHa和CaSki细胞的细胞质中,E6也与核糖核蛋白超微结构以及一些核糖体区域相关。在转染的HeLa细胞中表达的嵌合β-半乳糖苷酶-E6蛋白主要定位于核区室。总之,这些数据表明HPV-16的E6序列可能编码一个核定位信号。这种病毒癌蛋白在HPV转化细胞中的优先核分布与其在转录水平的活性相关。