CLONING AND EXPRESSION OF THE CDNA FOR E6-AP, A PROTEIN THAT MEDIATES THE INTERACTION OF THE HUMAN PAPILLOMAVIRUS E6 ONCOPROTEIN WITH P53

被引:474
作者
HUIBREGTSE, JM
SCHEFFNER, M
HOWLEY, PM
机构
[1] Laboratory of Tumor Virus Biology, National Cancer Institute, Bethesda
关键词
D O I
10.1128/MCB.13.2.775
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The E6 oncoproteins of the cancer-associated or high-risk human papillomaviruses (HPVs) target the cellular p53 protein. The association of E6 with p53 leads to the specific ubiquitination and degradation of p53 in vitro, suggesting a model by which E6 deregulates cell growth control by the elimination of the p53 tumor suppressor protein. Complex formation between E6 and p53 requires an additional cellular factor, designated E6-AP (E6-associated protein), which has a native and subunit molecular mass of approximately 100 kDa. Here we report the purification of E6-AP and the cloning of its corresponding cDNA, which contains a novel open reading frame encoding 865 amino acids. E6-AP, translated in vitro, has the following properties: (i) it associates with wild-type p53 in the presence of the HPV16 E6 protein and simultaneously stimulates the association of E6 with p53, (ii) it associates with the high-risk HPV16 and HPV18 E6 proteins in the absence of p53, and (iii) it induces the E6- and ubiquitin-dependent degradation of p53 in vitro.
引用
收藏
页码:775 / 784
页数:10
相关论文
共 49 条
[1]   SUPPRESSION OF HUMAN COLORECTAL-CARCINOMA CELL-GROWTH BY WILD-TYPE-P53 [J].
BAKER, SJ ;
MARKOWITZ, S ;
FEARON, ER ;
WILLSON, JKV ;
VOGELSTEIN, B .
SCIENCE, 1990, 249 (4971) :912-915
[2]   DEGRADATION OF NUCLEAR ONCOPROTEINS BY THE UBIQUITIN SYSTEM INVITRO [J].
CIECHANOVER, A ;
DIGIUSEPPE, JA ;
BERCOVICH, B ;
ORIAN, A ;
RICHTER, JD ;
SCHWARTZ, AL ;
BRODEUR, GM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (01) :139-143
[3]   HOW ARE SUBSTRATES RECOGNIZED BY THE UBIQUITIN-MEDIATED PROTEOLYTIC SYSTEM [J].
CIECHANOVER, A ;
SCHWARTZ, AL .
TRENDS IN BIOCHEMICAL SCIENCES, 1989, 14 (12) :483-488
[4]  
CROOK T, 1991, ONCOGENE, V6, P873
[5]   THE PRODUCT OF THE RETINOBLASTOMA SUSCEPTIBILITY GENE HAS PROPERTIES OF A CELL-CYCLE REGULATORY ELEMENT [J].
DECAPRIO, JA ;
LUDLOW, JW ;
LYNCH, D ;
FURUKAWA, Y ;
GRIFFIN, J ;
PIWNICAWORMS, H ;
HUANG, CM ;
LIVINGSTON, DM .
CELL, 1989, 58 (06) :1085-1095
[6]   P53 FUNCTIONS AS A CELL-CYCLE CONTROL PROTEIN IN OSTEOSARCOMAS [J].
DILLER, L ;
KASSEL, J ;
NELSON, CE ;
GRYKA, MA ;
LITWAK, G ;
GEBHARDT, M ;
BRESSAC, B ;
OZTURK, M ;
BAKER, SJ ;
VOGELSTEIN, B ;
FRIEND, SH .
MOLECULAR AND CELLULAR BIOLOGY, 1990, 10 (11) :5772-5781
[7]  
DURST M, 1987, ONCOGENE, V1, P251
[8]   THE HUMAN PAPILLOMA VIRUS-16 E7-ONCOPROTEIN IS ABLE TO BIND TO THE RETINOBLASTOMA GENE-PRODUCT [J].
DYSON, N ;
HOWLEY, PM ;
MUNGER, K ;
HARLOW, E .
SCIENCE, 1989, 243 (4893) :934-937
[9]   WILD-TYPE P53 CAN INHIBIT ONCOGENE-MEDIATED FOCUS FORMATION [J].
ELIYAHU, D ;
MICHALOVITZ, D ;
ELIYAHU, S ;
PINHASIKIMHI, O ;
OREN, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (22) :8763-8767
[10]   TUMORIGENIC POTENTIAL ASSOCIATED WITH ENHANCED EXPRESSION OF A GENE THAT IS AMPLIFIED IN A MOUSE-TUMOR CELL-LINE [J].
FAKHARZADEH, SS ;
TRUSKO, SP ;
GEORGE, DL .
EMBO JOURNAL, 1991, 10 (06) :1565-1569