×

zbMATH — the first resource for mathematics

A mathematical model of cell cycle dysregulation due to human papillomavirus infection. (English) Zbl 1372.92024
Summary: Human papillomaviruses (HPVs) that infect mucosal epithelium can be classified as high risk or low risk based on their propensity to cause lesions that can undergo malignant progression. HPVs produce the E7 protein that binds to cell cycle regulatory proteins including the retinoblastoma tumor suppressor protein (RB) to modulate cell cycle control. Generally, high-risk HPV E7 proteins bind to RB with a higher affinity than low-risk HPV E7s, but both are able to deactivate RB and trigger S phase progression. In uninfected cells, RB inactivation is a tightly controlled process that must coincide with growth factor stimulation to commit cells to division. High-risk HPV E7 proteins short-circuit this control by decreasing growth factor requirement for cell division. We develop a mathematical model to examine the role that RB binding affinity, growth factor concentration, and E7 concentration have on cell cycle progression. Our model predicts that high RB binding affinity and E7 concentration accelerate the \(\mathrm {G}_{1}\) to S phase transition and weaken the dependence on growth factor. This model thus captures a key step in high-risk HPV oncogenesis.
MSC:
92C37 Cell biology
92C60 Medical epidemiology
PDF BibTeX XML Cite
Full Text: DOI
References:
[1] Aoki, K; Yamada, M; Kunida, K; Yasuda, S; Matsuda, M, Processive phosphorylation of ERK MAP kinase in Mammalian cells, Proc Natl Acad Sci, 108, 12,675-12,680, (2011)
[2] Asih, TSN; Lenhart, S; Wise, S; Aryati, L; Adi-Kusumo, F; Hardianti, MS; Forde, J, The dynamics of HPV infection and cervical cancer cells, Bull Math Biol, 78, 4-20, (2016) · Zbl 1356.92055
[3] Barr, AR; Heldt, FS; Zhang, T; Bakal, C; Novák, B, A dynamical framework for the all-or-none G1/S transition, Cell Syst, 2, 27-37, (2016)
[4] Bernard, HU; Burk, RD; Chen, Z; Doorslaer, K; Hausen, H; Villiers, EM, Classification of papillomaviruses (PVs) based on 189 PV types and proposal of taxonomic amendments, Virology, 401, 70-79, (2010)
[5] Bertoli, C; Skotheim, JM; Bruin, RA, Control of cell cycle transcription during G1 and S phases, Nat Rev Mol Cell Biol, 14, 518-528, (2013)
[6] Biggin, MD, Animal transcription networks as highly connected, quantitative continua, Dev Cell, 21, 611-626, (2011)
[7] Bodily, J; Laimins, LA, Persistence of human papillomavirus infection: keys to malignant progression, Trends Microbiol, 19, 33-39, (2011)
[8] Chaturvedi, AK, Beyond cervical cancer: burden of other HPV-related cancers among men and women, J Adolesc Health, 46, s20-s26, (2010)
[9] Chemes, LB; Sánchez, IE; Smal, C; Prat-Gay, G, Targeting mechanism of the retinoblastoma tumor suppressor by a prototypical viral oncoprotein, FEBS J, 277, 973-988, (2010)
[10] Chemes, LB; Sánchez, IE; Prat-Gay, G, Kinetic recognition of the retinoblastoma tumor suppressor by a specific protein target, J Mol Biol, 412, 267-284, (2011)
[11] Chong, JL; Wenzel, PL; Sáenz-Robles, MT; Nair, V; Ferrey, A; Hagan, JP; Gomez, YM; Sharma, N; Chen, HZ; Ouseph, M; etal., E2f1-3 switch from activators in progenitor cells to repressors in differentiating cells, Nature, 462, 930-934, (2009)
[12] Chow, LT; Broker, TR; Steinberg, BM, The natural history of human papillomavirus infections of the mucosal epithelia, Apmis, 118, 422-449, (2010)
[13] Ciccolini, F; Pasquale, G; Carlotti, F; Crawford, L; Tommasino, M, Functional studies of E7 proteins from different HPV types, Oncogene, 9, 2633-2638, (1994)
[14] Clayton, E; Doupé, DP; Klein, AM; Winton, DJ; Simons, BD; Jones, PH, A single type of progenitor cell maintains normal epidermis, Nature, 446, 185-189, (2007)
[15] Diehl, JA; Cheng, M; Roussel, MF; Sherr, CJ, Glycogen synthase kinase-3\(β \) regulates cyclin D1 proteolysis and subcellular localization, Genes Dev, 12, 3499-3511, (1998)
[16] Doorbar, J, Molecular biology of human papillomavirus infection and cervical cancer, Clin Sci, 110, 525-541, (2006)
[17] Egawa, N; Doorbar, J, The low-risk papillomaviruses, Virus Res, 231, 119-127, (2016)
[18] Ekholm, SV; Reed, SI, Regulation of \({{\rm G}}_{1}\) cyclin-dependent kinases in the Mammalian cell cycle, Curr Opin Cell Biol, 12, 676-684, (2000)
[19] Elbasha, EH; Dasbach, EJ; Insinga, RP, Model for assessing human papillomavirus vaccination strategies, Emerg Infect Dis, 13, 28-41, (2007)
[20] Ferrell, JE, Self-perpetuating states in signal transduction: positive feedback, double-negative feedback and bistability, Curr Opin Cell Biol, 14, 140-148, (2002)
[21] Fujioka, A; Terai, K; Itoh, RE; Aoki, K; Nakamura, T; Kuroda, S; Nishida, E; Matsuda, M, Dynamics of the ras/ERK MAPK cascade as monitored by fluorescent probes, J Biol Chem, 281, 8917-8926, (2006)
[22] Giarrè, M; Caldeira, S; Malanchi, I; Ciccolini, F; Leão, MJ; Tommasino, M, Induction of prb degradation by the human papillomavirus type 16 E7 protein is essential to efficiently overcome p16INK4a-imposed G1 cell cycle arrest, J Virol, 75, 4705-4712, (2001)
[23] Gonzalez, SL; Stremlau, M; He, X; Basile, JR; Münger, K, Degradation of the retinoblastoma tumor suppressor by the human papillomavirus type 16 E7 oncoprotein is important for functional inactivation and is separable from proteasomal degradation of E7, J Virol, 75, 7583-7591, (2001)
[24] Goodwin, EC; DiMaio, D, Repression of human papillomavirus oncogenes in hela cervical carcinoma cells causes the orderly reactivation of dormant tumor suppressor pathways, Proc Nat Acad Sci, 97, 12,513-12,518, (2000)
[25] Groves, IJ; Coleman, N, Pathogenesis of human papillomavirus-associated mucosal disease, J Pathol, 235, 527-538, (2015)
[26] Hanahan, D; Weinberg, RA, The hallmarks of cancer, Cell, 100, 57-70, (2000)
[27] Heck, DV; Yee, CL; Howley, PM; Münger, K, Efficiency of binding the retinoblastoma protein correlates with the transforming capacity of the E7 oncoproteins of the human papillomaviruses, Proc Nat Acad Sci, 89, 4442-4446, (1992)
[28] Henley, SA; Dick, FA, The retinoblastoma family of proteins and their regulatory functions in the Mammalian cell division cycle, Cell Div, 7, 10, (2012)
[29] Huh, K; Zhou, X; Hayakawa, H; Cho, JY; Libermann, TA; Jin, J; Harper, JW; Munger, K, Human papillomavirus type 16 E7 oncoprotein associates with the cullin 2 ubiquitin ligase complex, which contributes to degradation of the retinoblastoma tumor suppressor, J Virol, 81, 9737-9747, (2007)
[30] Insinga, RP; Dasbach, EJ; Elbasha, EH; Liaw, KL; Barr, E, Incidence and duration of cervical human papillomavirus 6, 11, 16, and 18 infections in Young women: an evaluation from multiple analytic perspectives, Cancer Epidemiol Biomark Prev, 16, 709-715, (2007)
[31] Johnson, DG; Schwarz, JK; Cress, WD; Nevins, JR, Expression of transcription factor E2F1 induces quiescent cells to enter S phase, Nature, 365, 349-352, (1993)
[32] Jones, DL; Alani, RM; Münger, K, The human papillomavirus E7 oncoprotein can uncouple cellular differentiation and proliferation in human keratinocytes by abrogating \({{\rm p}}21^{Cip1}\)-mediated inhibition of cdk2, Genes Dev, 11, 2101-2111, (1997)
[33] Jung, HS; Rajasekaran, N; Ju, W; Shin, YK, Human papillomavirus: current and future rnai therapeutic strategies for cervical cancer, J Clin Med, 4, 1126-1155, (2015)
[34] Kennedy, EM; Kornepati, AV; Goldstein, M; Bogerd, HP; Poling, BC; Whisnant, AW; Kastan, MB; Cullen, BR, Inactivation of the human papillomavirus E6 or E7 gene in cervical carcinoma cells by using a bacterial CRISPR/cas RNA-guided endonuclease, J Virol, 88, 11,965-11,972, (2014)
[35] Klingelhutz, AJ; Roman, A, Cellular transformation by human papillomaviruses: lessons learned by comparing high-and low-risk viruses, Virology, 424, 77-98, (2012)
[36] Koutsky, L, Epidemiology of genital human papillomavirus infection, Am J Med, 102, 3-8, (1997)
[37] Lee, C; Chang, JH; Lee, HS; Cho, Y, Structural basis for the recognition of the E2F transactivation domain by the retinoblastoma tumor suppressor, Genes Dev, 16, 3199-3212, (2002)
[38] Löwhagen, G; Bolmstedt, A; Ryd, W; Voog, E, The prevalence of “high-risk” HPV types in penile condyloma-like lesions: correlation between HPV type and morphology, Genitourin Med, 69, 87-90, (1993)
[39] Ludlow, J; Glendening, C; Livingston, D; DeCarprio, J, Specific enzymatic dephosphorylation of the retinoblastoma protein, Mol Cell Biol, 13, 367-372, (1993)
[40] Meijer, CJ; Snijders, PJ; Brule, A, Screening for cervical cancer: should we test for infection with high-risk HPV?, Can Med Assoc J, 163, 535-538, (2000)
[41] Mesri, EA; Feitelson, MA; Munger, K, Human viral oncogenesis: a cancer hallmarks analysis, Cell Host Microbe, 15, 266-282, (2014)
[42] Moreau, P; Richardson, PG; Cavo, M; Orlowski, RZ; San Miguel, JF; Palumbo, A; Harousseau, JL, Proteasome inhibitors in multiple myeloma: 10 years later, Blood, 120, 947-959, (2012)
[43] Morgan DO (2007) The cell cycle: principles of control. New Science Press, London
[44] Münger, K; Baldwin, A; Edwards, KM; Hayakawa, H; Nguyen, CL; Owens, M; Grace, M; Huh, K, Mechanisms of human papillomavirus-induced oncogenesis, J Virol, 78, 11,451-11,460, (2004)
[45] Murall, CL; McCann, KS; Bauch, CT, Revising ecological assumptions about human papillomavirus interactions and type replacement, J Theor Biol, 350, 98-109, (2014) · Zbl 1412.92316
[46] Myers, ER; McCrory, DC; Nanda, K; Bastian, L; Matchar, DB, Mathematical model for the natural history of human papillomavirus infection and cervical carcinogenesis, Am J Epidemiol, 151, 1158-1171, (2000)
[47] Naetar, N; Soundarapandian, V; Litovchick, L; Goguen, KL; Sablina, AA; Bowman-Colin, C; Sicinski, P; Hahn, WC; DeCaprio, JA; Livingston, DM, PP2A-mediated regulation of ras signaling in G2 is essential for stable quiescence and normal G1 length, Mol Cell, 54, 932-945, (2014)
[48] Narasimha, AM; Kaulich, M; Shapiro, GS; Choi, YJ; Sicinski, P; Dowdy, SF, Cyclin D activates the rb tumor suppressor by mono-phosphorylation, Elife, 3, 872, (2014)
[49] Novak, B; Tyson, JJ, A model for restriction point control of the Mammalian cell cycle, J Theor Biol, 230, 563-579, (2004)
[50] O’leary, B; Finn, RS; Turner, NC, Treating cancer with selective CDK4/6 inhibitors, Nat Rev Clin Oncol, 13, 417-430, (2016)
[51] Oriel, J, Natural history of genital warts, Br J Vener Dis, 47, 1-13, (1971)
[52] Orlando, PA; Brown, JS; Gatenby, RA; Guliano, AR, The ecology of HPV lesions and the role of somatic evolution in their progression, J Infect Dis, 208, 394-402, (2013)
[53] Pagliarulo E (2014) Understanding the early events of human papillomavirus lesion formation. PhD thesis, MRC National Institute for Medical Research
[54] Park, S; Chung, S; Kim, KM; Jung, KC; Park, C; Hahm, ER; Yang, CH, Determination of binding constant of transcription factor myc-MAX/MAX-MAX and E-box DNA: the effect of inhibitors on the binding, Biochim Biophys Acta, 1670, 217-228, (2004)
[55] Pyeon, D; Pearce, SM; Lank, SM; Ahlquist, P; Lambert, PF, Establishment of human papillomavirus infection requires cell cycle progression, PLoS Pathog, 5, e1000,318, (2009)
[56] Richardson, H; Kelsall, G; Tellier, P; Voyer, H; Abrahamowicz, M; Ferenczy, A; Coutlée, F; Franco, EL, The natural history of type-specific human papillomavirus infections in female university students, Cancer Epidemiol Biomark Prev, 12, 485-490, (2003)
[57] Roberts, JN; Buck, CB; Thompson, CD; Kines, R; Bernardo, M; Choyke, PL; Lowy, DR; Schiller, JT, Genital transmission of HPV in a mouse model is potentiated by nonoxynol-9 and inhibited by carrageenan, Nat Med, 13, 857-861, (2007)
[58] Ryser, MD; Myers, ER; Durrett, R, HPV clearance and the neglected role of stochasticity, PLoS Comput Biol, 11, e1004,113, (2015)
[59] Schmitt, A; Harry, J; Rapp, B; Wettstein, F; Iftner, T, Comparison of the properties of the E6 and E7 genes of low-and high-risk cutaneous papillomaviruses reveals strongly transforming and high rb-binding activity for the E7 protein of the low-risk human papillomavirus type 1, J Virol, 68, 7051-7059, (1994)
[60] Soetaert, K, Rootsolve: nonlinear root finding, equilibrium and steady-state analysis of ordinary differential equations, R package, 1, 6, (2009)
[61] Soetaert K, Herman PM (2009) A practical guide to ecological modelling. Using R as a simulation platform. Springer, Berlin, ISBN 978-1-4020-8623-6
[62] Soetaert K, Petzoldt T, Setzer RW (2010) Solving differential equations in R: package deSolve. J Stat Softw 33(9):1-25, http://www.jstatsoft.org/v33/i09
[63] Southern, SA; Herrington, CS, Differential cell cycle regulation by low-and high-risk human papillomaviruses in low-grade squamous intraepithelial lesions of the cervix, Cancer Res, 58, 2941-2945, (1998)
[64] Stanley, MA, Epithelial cell responses to infection with human papillomavirus, Clin Microbiol Rev, 25, 215-222, (2012)
[65] Verma, M; Erwin, S; Abedi, V; Hontecillas, R; Hoops, S; Leber, A; Bassaganya-Riera, J; Ciupe, SM, Modeling the mechanisms by which HIV-associated immunosuppression influences HPV persistence at the oral mucosa, PLoS ONE, 12, e0168,133, (2017)
[66] Weinberg R (2013) The biology of cancer. Garland Science, New York
[67] White, EA; Sowa, ME; Tan, MJA; Jeudy, S; Hayes, SD; Santha, S; Münger, K; Harper, JW; Howley, PM, Systematic identification of interactions between host cell proteins and E7 oncoproteins from diverse human papillomaviruses, Proc Nat Acad Sci, 109, e260-e267, (2012)
[68] Won, KA; Reed, SI, Activation of cyclin E/CDK2 is coupled to site-specific autophosphorylation and ubiquitin-dependent degradation of cyclin E, EMBO J, 15, 4182-4193, (1996)
[69] Wu, EW; Clemens, K; Heck, D; Münger, K, The human papillomavirus E7 oncoprotein and the cellular transcription factor E2F bind to separate sites on the retinoblastoma tumor suppressor protein, J Virol, 67, 2402-2407, (1993)
[70] Wu, L; Timmers, C; Maiti, B; Saavedra, HI; Sang, L; Chong, GT; Nuckolls, F; Giangrande, P; Wright, FA; Field, SJ; etal., The E2F1-3 transcription factors are essential for cellular proliferation, Nature, 414, 457-462, (2001)
[71] Yao, G; Lee, TJ; Mori, S; Nevins, JR; You, L, A bistable rb-E2F switch underlies the restriction point, Nat Cell Biol, 10, 476-482, (2008)
[72] Zetterberg, A; Larsson, O, Kinetic analysis of regulatory events in G1 leading to proliferation or quiescence of swiss 3T3 cells, Proc Nat Acad Sci, 82, 5365-5369, (1985)
[73] Zheng, ZM; Baker, CC, Papillomavirus genome structure, expression, and post-transcriptional regulation, Front Biosci, 11, 2286-2302, (2006)
This reference list is based on information provided by the publisher or from digital mathematics libraries. Its items are heuristically matched to zbMATH identifiers and may contain data conversion errors. It attempts to reflect the references listed in the original paper as accurately as possible without claiming the completeness or perfect precision of the matching.