-
In this work, based on the Hill dynamics and Michaelis-Menten equation, a theoretical model is built to study the influence of time delay on the oscillation dynamics of a cyclin-dependent kinase 1 (CDK1)/ anaphase-promoting complex (APC) system. The theoretical model considers the time delay in the CDK1- polo-like protein kinase (P1K1)-APC pathway. We find that under different time delay conditions, the CDK1, Plk1 and APC exhibit periodic oscillation characteristics over time, indicating cell cycle progression. With the increase of time delay, the oscillation periods and amplitudes of CDK1, Plk1 and APC increase, which indicates that the time delay will change the dynamic characteristics of the system. It implies that during the cell cycle, the status of the CDK1/APC oscillation system will show a long-term correlation with the biochemical reaction time of each component, such as CDK1, Plk1 and APC. This correlation is influenced by its past, and there is a time-delay effect. The additional correction will be made due to time delay. By investigating the time-delay effect in Gaussian white noise environment, we find that in the Gaussian white noise environment, the noise disturbance obviously changes the dynamic characteristics of CDK1 evolution with time. In a low-noise environment, the CDK1/APC system changes the oscillation amplitude or period through self-adjusting time delay, so that the system can restore the stable periodic oscillation, while in a high noise environment, CDK1 exhibits a damped oscillation, indicating that the periodic oscillation dynamics of the CDK1/APC system will be significantly changed by strong noise. In the CDK1/APC system oscillation process, the system adjusts the physiological response through a feedback mechanism. There is a time delay between the perception of the noise effect and the establishment of an appropriate physiological response. By different time delays, the system can adjust complex non-periodic chaotic rhythms with different time delays, and recover to produce a stable periodic physiological process. Owing to the time delay, the CDK1/APC oscillation system changes from the original stable oscillation to a damped oscillation, but the original oscillation mode is difficult to recover. The theoretical results further reveal the time-delay effect in cell cycle processes such as Xenopus embryos, and provide a theoretical basis for designing pathway treatment plans that regulate cell cycle and block tumor transformation.
-
Keywords:
- time delay /
- oscillatory dynamics /
- cell cycle
[1] Hartwell L H, Weinert T A 1989 Science 246 629Google Scholar
[2] Murray A W, Kirschner M W 1989 Nature 339 275Google Scholar
[3] Ben-Sahra I, Howell J J, Asara J M, Manning B D 2013 Science 339 1323Google Scholar
[4] Loh X Y, Sun Q Y, Ding L W, Mayakonda A, Venkatachalam N, Yeo M S, Silva T C, Xiao J F, Doan N B, Said J W, Ran X B, Zhou S Q, Dakle P, Shyamsunder P, Koh A P F, Huang R Y J, Berman B, Tan S Y, Yang H, Lin D C, Koeffler H P 2019 Cancer Res. 80 219
[5] Goldbeter A 2002 Nature 420 238Google Scholar
[6] Chen K C, Calzone L, Csikasz-Nagy A, Cross F R, Novak B, Tyson J J 2004 Mol. Biol. Cell 15 3841Google Scholar
[7] Pines J 2011 Nat. Rev. Mol. Cell Biol. 12 427
[8] Kim S Y, Song E J, Lee K J, Ferrell J E 2005 Mol. Cell Biol. 25 10580Google Scholar
[9] Murray A W, Kirschner M W 1989 Science 246 614Google Scholar
[10] Sha W, Moore J, Chen K, Lassaletta A D, Yi C S, Tyson J J, Sible J C 2003 Proc. Natl. Acad. Sci. USA 100 975Google Scholar
[11] Dasso M, Newport J W 1990 Cell 61 811Google Scholar
[12] Minshull J, Sun H, Tonks N K, Murray A W 1994 Cell 79 475Google Scholar
[13] Hara K, Tydeman P, Kirschner M 1980 Proc. Natl. Acad. Sci. USA 77 462Google Scholar
[14] King R W, Peters J M, Tugendreich S, Rolfe M, Hieter P, Kirschner M W 1995 Cell 81 279Google Scholar
[15] Gao Z F, Shan H, Wang H 2021 Astron Nachr. 342 369Google Scholar
[16] Yang Q, Jr J E F 2013 Nat. Cell Biol. 15 518
[17] Doedel E J 1981 Cong. Numer. 30 265
[18] Novak B, Tyson J J 1993 J. Theor. Biol. 165 101Google Scholar
[19] Novak B, Tyson J J 1993 J. Cell Sci. 106 1153Google Scholar
[20] Srividhya J, Gopinathan M S 2006 J. Theor. Biol. 241 617Google Scholar
[21] Ferrell Jr J E, Tsai T Y C, Yang Q 2011 Cell 144 18874
[22] Bae H, Go Y H, Kwon T, Sung B J, Cha H Jin 2019 Pharm. Res. 36 1Google Scholar
[23] Seki A, Coppinger J A, Jang C Y, Yates J R, Fang G W 2008 Science 320 1655Google Scholar
[24] Glass L, Beuter A, Larocque D 1988 Math. Biosci. 90 111Google Scholar
[25] Zhang C, Du L P, WangT H, Yang T, Zeng C H, Wang C J 2017 Chaos, Solitons & Fractals 96 120
[26] Karamched B R, Bressloff P C 2015 Biophys. J. 108 2408Google Scholar
[27] Steuer R 2004 J. Theor. Biol. 228 293Google Scholar
[28] Kyrychko Y N and Schwartz I B 2018 Chaos 28 063106Google Scholar
[29] McAdams H H, Arkin A 1999 Trends Gene. 15 65Google Scholar
[30] Vilar J M G, Kueh H Y, Barkai N, Leibler S 2002 Proc. Natl. Acad. Sci. USA 99 5988Google Scholar
[31] Morrison J F, Walsh C T 1988 Adv. Enzymol. Relat. Areas. Mol. Biol. 61 201
[32] Roskoski R, Ritchie P A 2001 Biochemistry 40 9329Google Scholar
[33] Vodermaier H C 2004 Curr. Biol. 14 R787Google Scholar
[34] Zitouni S, Nabais C, Jana S C, Guerrero A, Bettencourt-Dias M 2014 Nat. Rev. Mol. Cell Biol. 15 433Google Scholar
[35] Glass D S, Jin X F, Riedel-Kruse I H 2021 Nat. Commun. 12 1Google Scholar
[36] Huang B, Tian X Y, Liu F, Wang W 2016 Phys. Rev. E 94 052413Google Scholar
[37] Ott W 2008 Comm. Math. Phys. 281 775Google Scholar
[38] Pomerening J R, Kim S Y, Ferrell J E 2005 Cell 122 565Google Scholar
[39] Lin K K, Young L S 2008 Nonlinearity 21 899Google Scholar
[40] Kuznetsov A P, Turukina L V, Mosekilde E 2001 Internat. J. Bifur. Chaos Appl. Sci. Engrg. 11 1065Google Scholar
-
图 4 不同
$ {\tau _{\text{A}}} $ 条件下,$ [{\text{CDK1}}] $ 与$ [{\text{APC}}] $ 对应的相图, 以及$ {\tau _{\text{A}}} = 2.0 $ 时,$ [{\text{CDK1}}] $ 与$ [{\text{APC}}] $ 随时间的演化Figure 4. Phase plots of
$ [{\text{CDK1}}] $ vs$ [{\text{APC}}] $ different$ {\tau _{\text{A}}} $ , and temporal evolutions of the levels of$ [{\text{CDK1}}] $ and$ [{\text{APC}}] $ for$ {\tau _{\text{A}}} = 2.0 $ . -
[1] Hartwell L H, Weinert T A 1989 Science 246 629Google Scholar
[2] Murray A W, Kirschner M W 1989 Nature 339 275Google Scholar
[3] Ben-Sahra I, Howell J J, Asara J M, Manning B D 2013 Science 339 1323Google Scholar
[4] Loh X Y, Sun Q Y, Ding L W, Mayakonda A, Venkatachalam N, Yeo M S, Silva T C, Xiao J F, Doan N B, Said J W, Ran X B, Zhou S Q, Dakle P, Shyamsunder P, Koh A P F, Huang R Y J, Berman B, Tan S Y, Yang H, Lin D C, Koeffler H P 2019 Cancer Res. 80 219
[5] Goldbeter A 2002 Nature 420 238Google Scholar
[6] Chen K C, Calzone L, Csikasz-Nagy A, Cross F R, Novak B, Tyson J J 2004 Mol. Biol. Cell 15 3841Google Scholar
[7] Pines J 2011 Nat. Rev. Mol. Cell Biol. 12 427
[8] Kim S Y, Song E J, Lee K J, Ferrell J E 2005 Mol. Cell Biol. 25 10580Google Scholar
[9] Murray A W, Kirschner M W 1989 Science 246 614Google Scholar
[10] Sha W, Moore J, Chen K, Lassaletta A D, Yi C S, Tyson J J, Sible J C 2003 Proc. Natl. Acad. Sci. USA 100 975Google Scholar
[11] Dasso M, Newport J W 1990 Cell 61 811Google Scholar
[12] Minshull J, Sun H, Tonks N K, Murray A W 1994 Cell 79 475Google Scholar
[13] Hara K, Tydeman P, Kirschner M 1980 Proc. Natl. Acad. Sci. USA 77 462Google Scholar
[14] King R W, Peters J M, Tugendreich S, Rolfe M, Hieter P, Kirschner M W 1995 Cell 81 279Google Scholar
[15] Gao Z F, Shan H, Wang H 2021 Astron Nachr. 342 369Google Scholar
[16] Yang Q, Jr J E F 2013 Nat. Cell Biol. 15 518
[17] Doedel E J 1981 Cong. Numer. 30 265
[18] Novak B, Tyson J J 1993 J. Theor. Biol. 165 101Google Scholar
[19] Novak B, Tyson J J 1993 J. Cell Sci. 106 1153Google Scholar
[20] Srividhya J, Gopinathan M S 2006 J. Theor. Biol. 241 617Google Scholar
[21] Ferrell Jr J E, Tsai T Y C, Yang Q 2011 Cell 144 18874
[22] Bae H, Go Y H, Kwon T, Sung B J, Cha H Jin 2019 Pharm. Res. 36 1Google Scholar
[23] Seki A, Coppinger J A, Jang C Y, Yates J R, Fang G W 2008 Science 320 1655Google Scholar
[24] Glass L, Beuter A, Larocque D 1988 Math. Biosci. 90 111Google Scholar
[25] Zhang C, Du L P, WangT H, Yang T, Zeng C H, Wang C J 2017 Chaos, Solitons & Fractals 96 120
[26] Karamched B R, Bressloff P C 2015 Biophys. J. 108 2408Google Scholar
[27] Steuer R 2004 J. Theor. Biol. 228 293Google Scholar
[28] Kyrychko Y N and Schwartz I B 2018 Chaos 28 063106Google Scholar
[29] McAdams H H, Arkin A 1999 Trends Gene. 15 65Google Scholar
[30] Vilar J M G, Kueh H Y, Barkai N, Leibler S 2002 Proc. Natl. Acad. Sci. USA 99 5988Google Scholar
[31] Morrison J F, Walsh C T 1988 Adv. Enzymol. Relat. Areas. Mol. Biol. 61 201
[32] Roskoski R, Ritchie P A 2001 Biochemistry 40 9329Google Scholar
[33] Vodermaier H C 2004 Curr. Biol. 14 R787Google Scholar
[34] Zitouni S, Nabais C, Jana S C, Guerrero A, Bettencourt-Dias M 2014 Nat. Rev. Mol. Cell Biol. 15 433Google Scholar
[35] Glass D S, Jin X F, Riedel-Kruse I H 2021 Nat. Commun. 12 1Google Scholar
[36] Huang B, Tian X Y, Liu F, Wang W 2016 Phys. Rev. E 94 052413Google Scholar
[37] Ott W 2008 Comm. Math. Phys. 281 775Google Scholar
[38] Pomerening J R, Kim S Y, Ferrell J E 2005 Cell 122 565Google Scholar
[39] Lin K K, Young L S 2008 Nonlinearity 21 899Google Scholar
[40] Kuznetsov A P, Turukina L V, Mosekilde E 2001 Internat. J. Bifur. Chaos Appl. Sci. Engrg. 11 1065Google Scholar
Catalog
Metrics
- Abstract views: 4547
- PDF Downloads: 91
- Cited By: 0