The E7 protein of the cottontail rabbit papillomavirus immortalizes normal rabbit keratinocytes and reduces pRb levels, while E6 cooperates in immortalization but neither degrades p53 nor binds E6AP

被引：19

作者：

Ganzenmueller, Tina ^{[1
]}

Matthaei, Markus ^{[1
]}

Muench, Peter ^{[1
]}

Scheible, Michael ^{[1
]}

Iftner, Angelika ^{[1
]}

Hiller, Thomas ^{[1
]}

Leiprecht, Natalie ^{[1
]}

Probst, Sonja ^{[1
]}

Stubenrauch, Frank ^{[1
]}

Iftner, Thomas ^{[1
]}

机构：

[1] Univ Klinikum Tuebingen, Sek Expt Virol, D-72076 Tubingen, Germany

来源：

VIROLOGY | 2008年 / 372卷 / 02期

关键词：

p53; protein; retinoblastoma protein; human papillomavirus; cottontail rabbit papillomavirus; E6; E7; keratinocytes; immortalization; rabbit; E6AP;

D O I：

10.1016/j.virol.2007.11.006

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Human papillomaviruses (HPVs) cause cervical cancer and are associated with the development of non-melanoma skin cancer. A suitable animal model for papillomavirus-associated skin carcinogenesis is the infection of domestic rabbits with the cottontail rabbit papillomavirus (CR-PV). As the immortalizing activity of CRPV genes in the natural target cells remains unknown, we investigated the properties of CRPV E6 and E7 in rabbit keratinocytes (RK) and their influence on the cell cycle. Interestingly, CRPV E7 immortalized RK after a cellular crisis but showed no such activity in human keratinocytes. Co-expressed CRPV E6 prevented cellular crisis. The HPV 16 or CRPV E7 protein reduced rabbit pRb levels thereby causing rabbit p19(ARF) induction and accumulation of p53 without affecting cellular proliferation. Both CRPV E6 proteins failed to degrade rabbit p53 in vitro or to bind E6AP; however, p53 was still inducible by mitomycin C. In summary, CRPV E7 immortalizes rabbit keratinocytes in a species-specific manner and E6 contributes to immortalization without directly affecting p53. (c) 2007 Elsevier Inc. All rights reserved.

引用

页码：313 / 324

页数：12

共 76 条

[1] Differential activation of p53 by the various adducts of mitomycin C [J].

Abbas, T ;

Olivier, M ;

Lopez, J ;

Houser, S ;

Xiao, G ;

Kumar, GS ;

Tomasz, M ;

Bargonetti, J .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (43) :40513-40519

[2]

ANANTHASWAMY HN, 1992, PROG CLIN BIOL RES, V376, P61

[3] p14ARF links the tumour suppressors RB and p53 [J].

Bates, S ;

Phillips, AC ;

Clark, PA ;

Stott, F ;

Peters, G ;

Ludwig, RL ;

Vousden, KH .

NATURE, 1998, 395 (6698) :124-125

[4] The risk of skin cancer in renal transplant recipients in Queensland, Australia [J].

Bavinck, JNB ;

Hardie, DR ;

Green, A ;

Cutmore, S ;

MacNaught, A ;

OSullivan, B ;

Siskind, V ;

VanDerWoude, FJ ;

Hardie, IR .

TRANSPLANTATION, 1996, 61 (05) :715-721

[5]

BAVNICK JNB, 2001, J INVEST DERMATOL, V6, P207

[6] The human papillomavirus E7 oncoprotein functionally interacts with the S4 subunit of the 26 S proteasome [J].

Berezutskaya, E ;

Bagchi, S .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (48) :30135-30140

[7] NESTED PCR APPROACH FOR DETECTION AND TYPING OF EPIDERMODYSPLASIA VERRUCIFORMIS-ASSOCIATED HUMAN PAPILLOMAVIRUS TYPES IN CUTANEOUS CANCERS FROM RENAL-TRANSPLANT RECIPIENTS [J].

BERKHOUT, RJM ;

TIEBEN, LM ;

SMITS, HL ;

BAVINCK, JNB ;

VERMEER, BJ ;

TERSCHEGGET, J .

JOURNAL OF CLINICAL MICROBIOLOGY, 1995, 33 (03) :690-695

[8]

BOSARI S, 1995, AM J PATHOL, V147, P790

[9]

Brandsma JL, 2005, METH MOLEC MED, V119, P217

[10] USE OF A RAPID, EFFICIENT INOCULATION METHOD TO INDUCE PAPILLOMAS BY COTTONTAIL RABBIT PAPILLOMAVIRUS DNA SHOWS THAT THE E7 GENE IS REQUIRED [J].

BRANDSMA, JL ;

YANG, ZH ;

BARTHOLD, SW ;

JOHNSON, EA .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (11) :4816-4820

← 1 2 3 4 5 6 7 8 →