Photo of Peter M. Howley,  MD

Peter M. Howley, MD

Harvard Medical School

Harvard Medical School
Phone: (617) 432-2889
Fax: (617) 432-2882


peter_howley@hms.harvard.edu

Peter M. Howley, MD

Harvard Medical School

EDUCATIONAL TITLES

  • Shattuck Professor of Pathological Anatomy, Pathology, Harvard Medical School
  • Professor, Microbiology and Immunobiology, Harvard Medical School

DF/HCC PROGRAM AFFILIATION

DF/HCC ASSOCIATIONS

  • Institutional Representative for HMS, Executive Committee
  • Member, Center Scientific Council
  • Associate Director, Program Development, Executive Committee

Research Abstract

The Howley laboratory studies the molecular biology of the papillomaviruses using the bovine papillomavirus (BPV) as well as the human papillomaviruses (HPVs). BPV is the most extensively studied of the papillomaviruses and has served as the model system for the analysis of viral transcription and of viral DNA replication. One focus of our studies has involved the viral E1 and E2 proteins and their roles in the regulation of viral transcription and DNA replication. We are conducting structure/function studies of the viral E1 and E2 proteins with the hope of developing inhibitors of their functions.


There are over 70 different HPVs, and some of them are associated with specific human cancers most notably human cervical cancer. We study the role of these HPVs in human neoplasia and the mechanisms by which these viruses contribute to cellular transformation. The virus encodes two proteins, E6 and E7, that have oncogenic properties and that contribute directly to HPV associated carcinogenesis. A particular focus of the laboratory is the study of the E6 gene, which has multiple functions, including the ability to functionally inactivate p53 by targeting its ubiquitination and proteolysis. This process is mediated by a cellular protein, E6AP, that binds to E6 and functions as a ubiquitin protein ligase in promoting the E6 dependent ubiquitination of p53. We are conducting structure/function studies on E6 and E6AP, and are studying additional functions of the papillomavirus E6 proteins. We have discovered that the BPV E6 protein binds to the cellular focal adhesion protein paxillin leading to a disruption of the actin cytoskeleton. We have also found that HPV16 E6 can bind IRF3 and inhibit its transcriptional activation function.

Publications

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  • White EA, Kramer RE, Hwang JH, Pores Fernando AT, Naetar N, Hahn WC, Roberts TM, Schaffhausen BS, Livingston DM, Howley PM. Papillomavirus E7 oncoproteins share functions with polyomavirus small T antigens. J Virol 2015; 89:2857-65. PubMed
  • Howley PM, Pfister HJ. Beta genus papillomaviruses and skin cancer. Virology 2015. PubMed
  • Galligan JT, Martinez-Noël G, Arndt V, Hayes S, Chittenden TW, Harper JW, Howley PM. Proteomic analysis and identification of cellular interactors of the giant ubiquitin ligase HERC2. J Proteome Res 2015; 14:953-66. PubMed
  • French CA, Rahman S, Walsh EM, Kuhnle S, Grayson AR, Lemieux ME, Grunfeld N, Rubin BP, Antonescu CR, Zhang S, Venkatramani R, Dal Cin P, Howley PM. NSD3-NUT Fusion Oncoprotein in NUT Midline Carcinoma: Implications for a Novel Oncogenic Mechanism. 2014. PubMed
  • White EA, Walther J, Javanbakht H, Howley PM. Genus Beta HPV E6 Proteins Vary in their Effects on the Transactivation of p53 Target Genes. J Virol 2014. PubMed
  • Vieira VC, Leonard B, White EA, Starrett GJ, Temiz NA, Lorenz LD, Lee D, Soares MA, Lambert PF, Howley PM, Harris RS. Human papillomavirus E6 triggers upregulation of the antiviral and cancer genomic DNA deaminase APOBEC3B. MBio 2014. PubMed
  • White EA, Kramer RE, Tan MJ, Hayes SD, Harper JW, Howley PM. Comprehensive analysis of host cellular interactions with human papillomavirus e6 proteins identifies new e6 binding partners and reflects viral diversity. J Virol 2012; 86:13174-86. PubMed
  • Martínez-Noël G, Galligan JT, Sowa ME, Arndt V, Overton TM, Harper JW, Howley PM. Identification and proteomic analysis of distinct UBE3A/E6AP protein complexes. Mol Cell Biol 2012; 32:3095-106. PubMed
  • Tan MJ, White EA, Sowa ME, Harper JW, Aster JC, Howley PM. Cutaneous 硫-human papillomavirus E6 proteins bind Mastermind-like coactivators and repress Notch signaling. Proc Natl Acad Sci U S A 2012; 109:E1473-80. PubMed
  • Powell ML, Smith JA, Sowa ME, Harper JW, Iftner T, Stubenrauch F, Howley PM. NCoR1 Mediates Papillomavirus E8;E2C Transcriptional Repression. J Virol 2010; 84:4451-60. PubMed
  • Smith JA, White EA, Sowa ME, Powell ML, Ottinger M, Harper JW, Howley PM. Genome-wide siRNA screen identifies SMCX, EP400, and Brd4 as E2-dependent regulators of human papillomavirus oncogene expression. Proc Natl Acad Sci U S A 2010; 107:3752-7. PubMed
  • Fradet-Turcotte A, Brault K, Titolo S, Howley PM, Archambault J. Characterization of papillomavirus E1 helicase mutants defective for interaction with the SUMO-conjugating enzyme Ubc9. Virology 2009; 395:190-201. PubMed
  • Ottinger M, Smith JA, Schweiger MR, Robbins D, Powell ML, You J, Howley PM. Cell-type specific transcriptional activities among different papillomavirus long control regions and their regulation by E2. Virology 2009; 395:161-71. PubMed
  • Zheng G, Schweiger MR, Martinez-Noel G, Zheng L, Smith JA, Harper JW, Howley PM. Brd4 regulation of papillomavirus protein E2 stability. J Virol 2009; 83:8683-92. PubMed
  • Vos RM, Altreuter J, White EA, Howley PM. The ubiquitin-specific peptidase USP15 regulates human papillomavirus type 16 E6 protein stability. J Virol 2009; 83:8885-92. PubMed
  • You J, Li Q, Wu C, Kim J, Ottinger M, Howley PM. Regulation of aurora B expression by the bromodomain protein Brd4. Mol Cell Biol 2009; 29:5094-103. PubMed
  • Howley PM,Livingston DM. Small DNA tumor viruses: large contributors to biomedical sciences. Virology 2009; 384:256-9. PubMed
  • Mulligan P,Westbrook TF,Ottinger M,Pavlova N,Chang B,Macia E,Shi YJ,Barretina J,Liu J,Howley PM,Elledge SJ,Shi Y. CDYL bridges REST and histone methyltransferases for gene repression and suppression of cellular transformation. Mol Cell 2008; 32:718-26. PubMed
  • Goh AM, Walters KJ, Elsasser S, Verma R, Deshaies RJ, Finley D, Howley PM. Components of the ubiquitin-proteasome pathway compete for surfaces on Rad23 family proteins. BMC Biochem 2008; 9:4. PubMed
  • Schweiger MR, Ottinger M, You J, Howley PM. Brd4-independent transcriptional repression function of the papillomavirus e2 proteins. J Virol 2007; 81:9612-22. PubMed
  • DeMasi J, Chao MC, Kumar AS, Howley PM. Bovine papillomavirus E7 oncoprotein inhibits anoikis. J Virol 2007; 81:9419-25. PubMed
  • Schweiger MR, You J, Howley PM. Bromodomain protein 4 mediates the papillomavirus E2 transcriptional activation function. J Virol 2006; 80:4276-85. PubMed
  • Li L, Li Z, Howley PM, Sacks DB. E6AP and calmodulin reciprocally regulate estrogen receptor stability. J Biol Chem 2005; 281:1978-85. PubMed
  • You J, Schweiger MR, Howley PM. Inhibition of e2 binding to brd4 enhances viral genome loss and phenotypic reversion of bovine papillomavirus-transformed cells. J Virol 2005; 79:14956-61. PubMed
  • Huh KW, DeMasi J, Ogawa H, Nakatani Y, Howley PM, M. Association of the human papillomavirus type 16 E7 oncoprotein with the 600-kDa retinoblastoma protein-associated factor, p600. Proc Natl Acad Sci U S A 2005; 102:11492-7. PubMed
  • DeMasi J, Huh KW, Nakatani Y, M. Bovine papillomavirus E7 transformation function correlates with cellular p600 protein binding. Proc Natl Acad Sci U S A 2005; 102:11486-91. PubMed
  • Kirshner JR, Karpova AY, Kops M, Howley PM. Identification of TRAIL as an interferon regulatory factor 3 transcriptional target. J Virol 2005; 79:9320-4. PubMed
  • Bossis I, Roden RB, Gambhira R, Yang R, Tagaya M, Howley PM, Meneses PI. Interaction of tSNARE syntaxin 18 with the papillomavirus minor capsid protein mediates infection. J Virol 2005; 79:6723-31. PubMed
  • Walters KJ, Goh AM, Wang Q, Wagner G, Howley PM. Ubiquitin family proteins and their relationship to the proteasome: a structural perspective. Biochim Biophys Acta 2004; 1695:73-87. PubMed
  • Cooper EM, Hudson AW, Amos J, Wagstaff J, Howley PM. Biochemical analysis of Angelman syndrome-associated mutations in the E3 ubiquitin ligase E6-associated protein (E6AP). J Biol Chem 2004; 279:41208-17. PubMed
  • You J, Croyle JL, Nishimura A, Ozato K, Howley PM. Interaction of the bovine papillomavirus E2 protein with Brd4 tethers the viral DNA to host mitotic chromosomes. Cell 2004; 117:349-60. PubMed
  • Hudson AW, Blom D, Howley PM, Ploegh HL. The ER-lumenal domain of the HHV-7 immunoevasin U21 directs class I MHC molecules to lysosomes. Traffic 2003; 4:824-37. PubMed
  • Wang Q, Goh AM, Howley PM, Walters KJ. Ubiquitin recognition by the DNA repair protein hHR23a. Biochemistry 2003; 42:13529-35. PubMed
  • Walters KJ, Lech PJ, Goh AM, Wang Q, Howley PM. DNA-repair protein hHR23a alters its protein structure upon binding proteasomal subunit S5a. Proc Natl Acad Sci U S A 2003; 100:12694-9. PubMed
  • Kleijnen MF, Alarcon RM, Howley PM. The ubiquitin-associated domain of hPLIC-2 interacts with the proteasome. Mol Biol Cell 2003; 14:3868-75. PubMed
  • Wells SI, Aronow BJ, Wise TM, Williams SS, Couget JA, Howley PM. Transcriptome signature of irreversible senescence in human papillomavirus-positive cervical cancer cells. Proc Natl Acad Sci U S A 2003; 100:7093-8. PubMed
  • M. Human papillomavirus immortalization and transformation functions. Virus Res 2002; 89:213-28. PubMed
  • Karpova AY, Trost M, Murray JM, Cantley LC, Howley PM. Interferon regulatory factor-3 is an in vivo target of DNA-PK. Proc Natl Acad Sci U S A 2002; 99:2818-23. PubMed
  • Walters KJ, Kleijnen MF, Goh AM, Wagner G, Howley PM. Structural studies of the interaction between ubiquitin family proteins and proteasome subunit S5a. Biochemistry 2002; 41:1767-77. PubMed
  • Hudson AW, Howley PM, Ploegh HL. A human herpesvirus 7 glycoprotein, U21, diverts major histocompatibility complex class I molecules to lysosomes. J Virol 2001; 75:12347-58. PubMed
  • Karpova AY, Ronco LV, Howley PM. Functional characterization of interferon regulatory factor 3a (IRF-3a), an alternative splice isoform of IRF-3. Mol Cell Biol 2001; 21:4169-76. PubMed
  • Karpova AY, Howley PM, Ronco LV. Dual utilization of an acceptor/donor splice site governs the alternative splicing of the IRF-3 gene. Genes Dev 2000; 14:2813-8. PubMed
  • Wells SI, Francis DA, Karpova AY, Dowhanick JJ, Benson JD, Howley PM. Papillomavirus E2 induces senescence in HPV-positive cells via pRB- and p21(CIP)-dependent pathways. EMBO J 2000; 19:5762-71. PubMed
  • Zhou P, Bogacki R, McReynolds L, Howley PM. Harnessing the ubiquitination machinery to target the degradation of specific cellular proteins. Mol Cell 2000; 6:751-6. PubMed
  • Kleijnen MF, Shih AH, Zhou P, Kumar S, Soccio RE, Kedersha NL, Gill G, Howley PM. The hPLIC proteins may provide a link between the ubiquitination machinery and the proteasome. Mol Cell 2000; 6:409-19. PubMed
  • Kao WH, Beaudenon SL, Talis AL, Huibregtse JM, Howley PM. Human papillomavirus type 16 E6 induces self-ubiquitination of the E6AP ubiquitin-protein ligase. J Virol 2000; 74:6408-17. PubMed
  • Bellamy SJ, Gibberd R, Hancock L, Howley P, Kennedy B, Klar N, Lipsitz S, Ryan L. Analysis of dichotomous outcome data for community intervention studies. Stat Methods Med Res 2000; 9:135-159.
  • Nishimura A, Ono T, Ishimoto A, Dowhanick JJ, Frizzell MA, Howley PM, Sakai H. Mechanisms of human papillomavirus E2-mediated repression of viral oncogene expression and cervical cancer cell growth inhibition. J Virol 2000; 74:3752-60. PubMed
  • Francis DA, Schmid SI, Howley PM. Repression of the integrated papillomavirus E6/E7 promoter is required for growth suppression of cervical cancer cells. J Virol 2000; 74:2679-86. PubMed
  • Harris KF, Shoji I, Cooper EM, Kumar S, Oda H, Howley PM. Ubiquitin-mediated degradation of active Src tyrosine kinase. Proc Natl Acad Sci U S A 1999; 96:13738-43. PubMed
  • Huang L, Kinnucan E, Wang G, Beaudenon S, Howley PM, Huibregtse JM, Pavletich NP. Structure of an E6AP-UbcH7 complex: insights into ubiquitination by the E2-E3 enzyme cascade. Science 1999; 286:1321-6. PubMed
  • Oda H, Kumar S, Howley PM. Regulation of the Src family tyrosine kinase Blk through E6AP-mediated ubiquitination. Proc Natl Acad Sci U S A 1999; 96:9557-62. PubMed
  • Kumar S, Talis AL, Howley PM. Identification of HHR23A as a substrate for E6-associated protein-mediated ubiquitination. J Biol Chem 1999; 274:18785-92. PubMed
  • Unger T, Sionov RV, Moallem E, Yee CL, Howley PM, Oren M, Haupt Y. Mutations in serines 15 and 20 of human p53 impair its apoptotic activity. Oncogene 1999; 18:3205-12. PubMed
  • Benson JD, Benson M, Howley PM, Struhl K. Association of distinct yeast Not2 functional domains with components of Gcn5 histone acetylase and Ccr4 transcriptional regulatory complexes. EMBO J 1998; 17:6714-22. PubMed
  • Zhou P, Howley PM. Ubiquitination and degradation of the substrate recognition subunits of SCF ubiquitin-protein ligases. Mol Cell 1998; 2:571-80. PubMed
  • Grossman SR, Perez M, Kung AL, Joseph M, Mansur C, Xiao ZX, Kumar S, Howley PM, Livingston DM. p300/MDM2 complexes participate in MDM2-mediated p53 degradation. Mol Cell 1998; 2:405-15. PubMed
  • Kasukawa H, Howley PM, Benson JD. A fifteen-amino-acid peptide inhibits human papillomavirus E1-E2 interaction and human papillomavirus DNA replication in vitro. J Virol 1998; 72:8166-73. PubMed
  • Patrick GN, Zhou P, Kwon YT, Howley PM, Tsai LH. p35, the neuronal-specific activator of cyclin-dependent kinase 5 (Cdk5) is degraded by the ubiquitin-proteasome pathway. J Biol Chem 1998; 273:24057-64. PubMed
  • Ronco LV, Karpova AY, Vidal M, Howley PM. Human papillomavirus 16 E6 oncoprotein binds to interferon regulatory factor-3 and inhibits its transcriptional activity. Genes Dev 1998; 12:2061-72. PubMed
  • Talis AL, Huibregtse JM, Howley PM. The role of E6AP in the regulation of p53 protein levels in human papillomavirus (HPV)-positive and HPV-negative cells. J Biol Chem 1998; 273:6439-45. PubMed
  • Wathelet MG, Lin CH, Parekh BS, Ronco LV, Howley PM, Maniatis T. Virus infection induces the assembly of coordinately activated transcription factors on the IFN-beta enhancer in vivo. Mol Cell 1998; 1:507-18. PubMed
  • Tong X, Boll W, Kirchhausen T, Howley PM. Interaction of the bovine papillomavirus E6 protein with the clathrin adaptor complex AP-1. J Virol 1998; 72:476-82. PubMed
  • Tong X, Salgia R, Li JL, Griffin JD, Howley PM. The bovine papillomavirus E6 protein binds to the LD motif repeats of paxillin and blocks its interaction with vinculin and the focal adhesion kinase. J Biol Chem 1998; 272:33373-6. PubMed
  • Benson JD, Lawande R, Howley PM. Conserved interaction of the papillomavirus E2 transcriptional activator proteins with human and yeast TFIIB proteins. J Virol 1997; 71:8041-7. PubMed
  • Yasugi T, Vidal M, Sakai H, Howley PM, Benson JD. Two classes of human papillomavirus type 16 E1 mutants suggest pleiotropic conformational constraints affecting E1 multimerization, E2 interaction, and interaction with cellular proteins. J Virol 1997; 71:5942-51. PubMed
  • Kumar S, Kao WH, Howley PM. Physical interaction between specific E2 and Hect E3 enzymes determines functional cooperativity. J Biol Chem 1997; 272:13548-54. PubMed
  • Tong X, Howley PM. The bovine papillomavirus E6 oncoprotein interacts with paxillin and disrupts the actin cytoskeleton. Proc Natl Acad Sci U S A 1997; 94:4412-7. PubMed
  • Yamamoto Y, Huibregtse JM, Howley PM. The human E6-AP gene (UBE3A) encodes three potential protein isoforms generated by differential splicing. Genomics 1997; 41:263-6. PubMed
  • Yasugi T, Benson JD, Sakai H, Vidal M, Howley PM. Mapping and characterization of the interaction domains of human papillomavirus type 16 E1 and E2 proteins. J Virol 1997; 71:891-9. PubMed
  • Howley PM, Gatehouse JA. A 38 bp repeat sequence within the pea seed storage protein promoter of legA is a binding site for a nuclear DNA-binding protein. Plant Mol Biol 1997; 33:175-80. PubMed
  • Maki CG, Howley PM. Ubiquitination of p53 and p21 is differentially affected by ionizing and UV radiation. Mol Cell Biol 1997; 17:355-63. PubMed
  • Maki CG, Huibregtse JM, Howley PM. In vivo ubiquitination and proteasome-mediated degradation of p53(1). Cancer Res 1996; 56:2649-54. PubMed
  • Yasugi T, Howley PM. Identification of the structural and functional human homolog of the yeast ubiquitin conjugating enzyme UBC9. Nucleic Acids Res 1996; 24:2005-10. PubMed
  • Khleif SN, DeGregori J, Yee CL, Otterson GA, Kaye FJ, Nevins JR, Howley PM. Inhibition of cyclin D-CDK4/CDK6 activity is associated with an E2F-mediated induction of cyclin kinase inhibitor activity. Proc Natl Acad Sci U S A 1996; 93:4350-4. PubMed
  • Arbeit JM, Howley PM, Hanahan D. Chronic estrogen-induced cervical and vaginal squamous carcinogenesis in human papillomavirus type 16 transgenic mice. Proc Natl Acad Sci U S A 1996; 93:2930-5. PubMed
  • Sakai H, Yasugi T, Benson JD, Dowhanick JJ, Howley PM. Targeted mutagenesis of the human papillomavirus type 16 E2 transactivation domain reveals separable transcriptional activation and DNA replication functions. J Virol 1996; 70:1602-11. PubMed
  • Dowhanick JJ, McBride AA, Howley PM. Suppression of cellular proliferation by the papillomavirus E2 protein. J Virol 1995; 69:7791-9. PubMed
  • Benson JD, Howley PM. Amino-terminal domains of the bovine papillomavirus type 1 E1 and E2 proteins participate in complex formation. J Virol 1995; 69:4364-72. PubMed
  • Huibregtse JM, Scheffner M, Beaudenon S, Howley PM. A family of proteins structurally and functionally related to the E6-AP ubiquitin-protein ligase. Proc Natl Acad Sci U S A 1995; 92:5249. PubMed
  • Huibregtse JM, Scheffner M, Beaudenon S, Howley PM. A family of proteins structurally and functionally related to the E6-AP ubiquitin-protein ligase. Proc Natl Acad Sci U S A 1995; 92:2563-7. PubMed
  • Vande Pol SB, Howley PM. Negative regulation of the bovine papillomavirus E5, E6, and E7 oncogenes by the viral E1 and E2 genes. J Virol 1995; 69:395-402. PubMed
  • Scheffner M, Huibregtse JM, Howley PM. Identification of a human ubiquitin-conjugating enzyme that mediates the E6-AP-dependent ubiquitination of p53. Proc Natl Acad Sci U S A 1994; 91:8797-801. PubMed
  • Arbeit JM, M. Progressive squamous epithelial neoplasia in K14-human papillomavirus type 16 transgenic mice. J Virol 1994; 68:4358-68. PubMed
  • Huibregtse JM, Scheffner M, Howley PM. E6-AP directs the HPV E6-dependent inactivation of p53 and is representative of a family of structurally and functionally related proteins. Cold Spring Harb Symp Quant Biol 1994; 59:237-45. PubMed
  • Scheffner M, Romanczuk H, M. Functions of human papillomavirus proteins. Curr Top Microbiol Immunol 1994; 186:83-99. PubMed
  • Scheffner M, Huibregtse JM, Vierstra RD, Howley PM. The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53. Cell 1993; 75:495-505. PubMed
  • Unger T, Mietz JA, Scheffner M, Yee CL, Howley PM. Functional domains of wild-type and mutant p53 proteins involved in transcriptional regulation, transdominant inhibition, and transformation suppression. Mol Cell Biol 1993; 13:5186-94. PubMed
  • Huibregtse JM, Scheffner M, Howley PM. Localization of the E6-AP regions that direct human papillomavirus E6 binding, association with p53, and ubiquitination of associated proteins. Mol Cell Biol 1993; 13:4918-27. PubMed
  • Arbeit JM, M. Neuroepithelial carcinomas in mice transgenic with human papillomavirus type 16 E6/E7 ORFs. Am J Pathol 1993; 142:1187-97. PubMed
  • Huibregtse JM, Scheffner M, Howley PM. Cloning and expression of the cDNA for E6-AP, a protein that mediates the interaction of the human papillomavirus E6 oncoprotein with p53. Mol Cell Biol 1993; 13:775-84. PubMed
  • Mietz JA, Unger T, Huibregtse JM, Howley PM. The transcriptional transactivation function of wild-type p53 is inhibited by SV40 large T-antigen and by HPV-16 E6 oncoprotein. EMBO J 1992; 11:5013-20. PubMed
  • Del Vecchio AM, Romanczuk H, Howley PM, Baker CC. Transient replication of human papillomavirus DNAs. J Virol 1992; 66:5949-58. PubMed
  • McBride AA, Klausner RD, Howley PM. Conserved cysteine residue in the DNA-binding domain of the bovine papillomavirus type 1 E2 protein confers redox regulation of the DNA-binding activity in vitro. Proc Natl Acad Sci U S A 1992; 89:7531-5. PubMed
  • Lichy JH, Modi WS, Seuanez HN, Howley PM. Identification of a human chromosome 11 gene which is differentially regulated in tumorigenic and nontumorigenic somatic cell hybrids of HeLa cells. Cell Growth Differ 1992; 3:541-8. PubMed
  • Scheffner M, Takahashi T, Huibregtse JM, Minna JD, Howley PM. Interaction of the human papillomavirus type 16 E6 oncoprotein with wild-type and mutant human p53 proteins. J Virol 1992; 66:5100-5. PubMed
  • Scheffner M, M. Targeted degradation of the retinoblastoma protein by human papillomavirus E7-E6 fusion proteins. EMBO J 1992; 11:2425-31. PubMed
  • Thierry F, Spyrou G, Yaniv M, Howley P. Two AP1 sites binding JunB are essential for human papillomavirus type 18 transcription in keratinocytes. J Virol 1992; 66:3740-8. PubMed
  • Chellappan S, Kraus VB, Kroger B, Munger K, Howley PM, Phelps WC, Nevins JR. Adenovirus E1A, simian virus 40 tumor antigen, and human papillomavirus E7 protein share the capacity to disrupt the interaction between transcription factor E2F and the retinoblastoma gene product. Proc Natl Acad Sci U S A 1992; 89:4549-53. PubMed
  • Heck DV, Yee CL, Howley PM, M. Efficiency of binding the retinoblastoma protein correlates with the transforming capacity of the E7 oncoproteins of the human papillomaviruses. Proc Natl Acad Sci U S A 1992; 89:4442-6. PubMed
  • Vande Pol SB, Howley PM. The bovine papillomavirus constitutive enhancer is essential for viral transformation, DNA replication, and the maintenance of latency. J Virol 1992; 66:2346-58. PubMed
  • Phelps WC, M. Structure-function analysis of the human papillomavirus type 16 E7 oncoprotein. J Virol 1992; 66:2418-27. PubMed
  • Romanczuk H, Howley PM. Disruption of either the E1 or the E2 regulatory gene of human papillomavirus type 16 increases viral immortalization capacity. Proc Natl Acad Sci U S A 1992; 89:3159-63. PubMed
  • M. Interactions of HPV E6 and E7 oncoproteins with tumour suppressor gene products. Cancer Surv 1992; 12:197-217. PubMed
  • Phelps WC, Bagchi S, Barnes JA, Raychaudhuri P, Kraus V, M. Analysis of trans activation by human papillomavirus type 16 E7 and adenovirus 12S E1A suggests a common mechanism. J Virol 1991; 65:6922-30. PubMed
  • McBride AA, Howley PM. Bovine papillomavirus with a mutation in the E2 serine 301 phosphorylation site replicates at a high copy number. J Virol 1991; 65:6528-34. PubMed
  • Huibregtse JM, Scheffner M, Howley PM. A cellular protein mediates association of p53 with the E6 oncoprotein of human papillomavirus types 16 or 18. EMBO J 1991; 10:4129-35. PubMed
  • Pietenpol JA, M. Factor-binding element in the human c-myc promoter involved in transcriptional regulation by transforming growth factor beta 1 and by the retinoblastoma gene product. Proc Natl Acad Sci U S A 1991; 88:10227-31. PubMed
  • McBride AA, Romanczuk H, Howley PM. The papillomavirus E2 regulatory proteins. J Biol Chem 1991; 266:18411-4. PubMed
  • Howley PM. Role of the human papillomaviruses in human cancer. Cancer Res 1991; 51:5019s-5022s. PubMed
  • Dostatni N, Lambert PF, Sousa R, Ham J, Howley PM, Yaniv M. The functional BPV-1 E2 trans-activating protein can act as a repressor by preventing formation of the initiation complex. Genes Dev 1991; 5:1657-71. PubMed
  • Scheffner M, M. The state of the p53 and retinoblastoma genes in human cervical carcinoma cell lines. Proc Natl Acad Sci U S A 1991; 88:5523-7. PubMed
  • M. Biochemical and biological differences between E7 oncoproteins of the high- and low-risk human papillomavirus types are determined by amino-terminal sequences. J Virol 1991; 65:3943-8. PubMed
  • Romanczuk H, Villa LL, Schlegel R, Howley PM. The viral transcriptional regulatory region upstream of the E6 and E7 genes is a major determinant of the differential immortalization activities of human papillomavirus types 16 and 18. J Virol 1991; 65:2739-44. PubMed
  • Schiffman MH, Bauer HM, Lorincz AT, Manos MM, Byrne JC, Glass AG, Cadell DM, Howley PM. Comparison of Southern blot hybridization and polymerase chain reaction methods for the detection of human papillomavirus DNA. J Clin Microbiol 1991; 29:573-7. PubMed
  • Howley PM, Levine AJ, Li FP, Livingston DM, Rabson AS. Lack of SV40 DNA in tumors from scientists working with SV40 virus. N Engl J Med 1991; 324:494. PubMed
  • Spalholz BA, Vande Pol SB, Howley PM. Characterization of the cis elements involved in basal and E2-transactivated expression of the bovine papillomavirus P2443 promoter. J Virol 1991; 65:743-53. PubMed
  • Howley PM. Tumor progression in transgenic mice containing the bovine papillomavirus genome. Basic Life Sci 1991; 57:103-7; discussion 108-10. PubMed
  • Howley PM, Scheffner M, Huibregtse J, M. Oncoproteins encoded by the cancer-associated human papillomaviruses target the products of the retinoblastoma and p53 tumor suppressor genes. Cold Spring Harb Symp Quant Biol 1991; 56:149-55. PubMed
  • Murphy CS, Pietenpol JA, M. c-myc and pRB: role in TGF-beta 1 inhibition of keratinocyte proliferation. Cold Spring Harb Symp Quant Biol 1991; 56:129-35. PubMed
  • Werness BA, M. Role of the human papillomavirus oncoproteins in transformation and carcinogenic progression. Important Adv Oncol 1991. PubMed
  • Howley PM, M. Cellular targets of the oncoproteins encoded by the cancer associated human papillomaviruses. Virus Res 1991; 22:239-48. PubMed
  • Thierry F, Howley PM. Functional analysis of E2-mediated repression of the HPV18 P105 promoter. New Biol 1991; 3:90-100. PubMed
  • Scheffner M, Werness BA, Huibregtse JM, Levine AJ, Howley PM. The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell 1990; 63:1129-36. PubMed
  • Vande Pol SB, Howley PM. A bovine papillomavirus constitutive enhancer is negatively regulated by the E2 repressor through competitive binding for a cellular factor. J Virol 1990; 64:5420-9. PubMed
  • Pietenpol JA, Stein RW, Moran E, Yaciuk P, Schlegel R, Lyons RM, Pittelkow MR, M. TGF-beta 1 inhibition of c-myc transcription and growth in keratinocytes is abrogated by viral transforming proteins with pRB binding domains. Cell 1990; 61:777-85. PubMed
  • Romanczuk H, Thierry F, Howley PM. Mutational analysis of cis elements involved in E2 modulation of human papillomavirus type 16 P97 and type 18 P105 promoters. J Virol 1990; 64:2849-59. PubMed
  • Werness BA, Levine AJ, Howley PM. Association of human papillomavirus types 16 and 18 E6 proteins with p53. Science 1990; 248:76-9. PubMed
  • Lambert PF, Monk BC, Howley PM. Phenotypic analysis of bovine papillomavirus type 1 E2 repressor mutants. J Virol 1990; 64:950-6. PubMed
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