#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Efficient Parvovirus Replication Requires CRL4-Targeted Depletion of p21 to Prevent Its Inhibitory Interaction with PCNA


Many DNA viruses induce and then exploit host cellular DNA damage responses to generate a suitable environment for their continued replication. Parvoviruses, important disease agents in both humans and animals, rely on host DNA polymerases to replicate their genomes in cell-cycle arrested cells. We show that efficient parvovirus replication requires the recruitment to viral replication compartments of a host cellular E3-ubiquitin ligase, CRL4Cdt2, to target the potent cell cycle regulator p21 for subsequent degradation. The DNA polymerase-δ cofactor PCNA provides a molecular platform for initial substrate recognition by this ligase, and subsequent p21 depletion prevents its continued interaction with PCNA which otherwise inhibits efficient viral replication. Virally-induced p21 degradation represents another way of promoting efficient replication of DNA polymerase-δ-dependent viruses.


Vyšlo v časopise: Efficient Parvovirus Replication Requires CRL4-Targeted Depletion of p21 to Prevent Its Inhibitory Interaction with PCNA. PLoS Pathog 10(4): e32767. doi:10.1371/journal.ppat.1004055
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004055

Souhrn

Many DNA viruses induce and then exploit host cellular DNA damage responses to generate a suitable environment for their continued replication. Parvoviruses, important disease agents in both humans and animals, rely on host DNA polymerases to replicate their genomes in cell-cycle arrested cells. We show that efficient parvovirus replication requires the recruitment to viral replication compartments of a host cellular E3-ubiquitin ligase, CRL4Cdt2, to target the potent cell cycle regulator p21 for subsequent degradation. The DNA polymerase-δ cofactor PCNA provides a molecular platform for initial substrate recognition by this ligase, and subsequent p21 depletion prevents its continued interaction with PCNA which otherwise inhibits efficient viral replication. Virally-induced p21 degradation represents another way of promoting efficient replication of DNA polymerase-δ-dependent viruses.


Zdroje

1. AdeyemiRO, LandryS, DavisME, WeitzmanMD, PintelDJ (2010) Parvovirus minute virus of mice induces a DNA damage response that facilitates viral replication. PLoS Pathog 6: e1001141.

2. AdeyemiRO, PintelDJ (2012) Replication of minute virus of mice in murine cells is facilitated by virally induced depletion of p21. J Virol 86: 8328–8332.

3. Op De BeeckA, Sobczak-ThepotJ, SirmaH, BourgainF, BrechotC, et al. (2001) NS1- and minute virus of mice-induced cell cycle arrest: involvement of p53 and p21(cip1). J Virol 75: 11071–11078.

4. AbbasT, DuttaA (2009) p21 in cancer: intricate networks and multiple activities. Nat Rev Cancer 9: 400–414.

5. ChenJ, JacksonPK, KirschnerMW, DuttaA (1995) Separate domains of p21 involved in the inhibition of Cdk kinase and PCNA. Nature 374: 386–388.

6. ChenJ, PetersR, SahaP, LeeP, TheodorasA, et al. (1996) A 39 amino acid fragment of the cell cycle regulator p21 is sufficient to bind PCNA and partially inhibit DNA replication in vivo. Nucleic Acids Res 24: 1727–1733.

7. WagaS, HannonGJ, BeachD, StillmanB (1994) The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA. Nature 369: 574–578.

8. BashirT, HorleinR, RommelaereJ, WillwandK (2000) Cyclin A activates the DNA polymerase delta -dependent elongation machinery in vitro: A parvovirus DNA replication model. Proc Natl Acad Sci U S A 97: 5522–5527.

9. RandowF, LehnerPJ (2009) Viral avoidance and exploitation of the ubiquitin system. Nat Cell Biol 11: 527–534.

10. AbbasT, SivaprasadU, TeraiK, AmadorV, PaganoM, et al. (2008) PCNA-dependent regulation of p21 ubiquitylation and degradation via the CRL4Cdt2 ubiquitin ligase complex. Genes Dev 22: 2496–2506.

11. KimY, StarostinaNG, KipreosET (2008) The CRL4Cdt2 ubiquitin ligase targets the degradation of p21Cip1 to control replication licensing. Genes Dev 22: 2507–2519.

12. NishitaniH, ShiomiY, IidaH, MichishitaM, TakamiT, et al. (2008) CDK inhibitor p21 is degraded by a proliferating cell nuclear antigen-coupled Cul4-DDB1Cdt2 pathway during S phase and after UV irradiation. J Biol Chem 283: 29045–29052.

13. HavensCG, WalterJC (2011) Mechanism of CRL4(Cdt2), a PCNA-dependent E3 ubiquitin ligase. Genes Dev 25: 1568–1582.

14. SoriaG, GottifrediV (2010) PCNA-coupled p21 degradation after DNA damage: The exception that confirms the rule? DNA Repair (Amst) 9: 358–364.

15. AbbasT, ShibataE, ParkJ, JhaS, KarnaniN, et al. (2010) CRL4(Cdt2) regulates cell proliferation and histone gene expression by targeting PR-Set7/Set8 for degradation. Mol Cell 40: 9–21.

16. CentoreRC, HavensCG, ManningAL, LiJM, FlynnRL, et al. (2010) CRL4(Cdt2)-mediated destruction of the histone methyltransferase Set8 prevents premature chromatin compaction in S phase. Mol Cell 40: 22–33.

17. JinJ, AriasEE, ChenJ, HarperJW, WalterJC (2006) A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, which is required for S phase destruction of the replication factor Cdt1. Mol Cell 23: 709–721.

18. BashirT, RommelaereJ, CziepluchC (2001) In vivo accumulation of cyclin A and cellular replication factors in autonomous parvovirus minute virus of mice-associated replication bodies. J Virol 75: 4394–4398.

19. CziepluchC, LampelS, GrewenigA, GrundC, LichterP, et al. (2000) H-1 parvovirus-associated replication bodies: a distinct virus-induced nuclear structure. J Virol 74: 4807–4815.

20. AmadorV, GeS, SantamariaPG, GuardavaccaroD, PaganoM (2007) APC/C(Cdc20) controls the ubiquitin-mediated degradation of p21 in prometaphase. Mol Cell 27: 462–473.

21. HavensCG, ShobnamN, GuarinoE, CentoreRC, ZouL, et al. (2012) Direct role for proliferating cell nuclear antigen in substrate recognition by the E3 ubiquitin ligase CRL4Cdt2. J Biol Chem 287: 11410–11421.

22. HavensCG, WalterJC (2009) Docking of a specialized PIP Box onto chromatin-bound PCNA creates a degron for the ubiquitin ligase CRL4Cdt2. Mol Cell 35: 93–104.

23. BendjennatM, BoulaireJ, JascurT, BricknerH, BarbierV, et al. (2003) UV irradiation triggers ubiquitin-dependent degradation of p21(WAF1) to promote DNA repair. Cell 114: 599–610.

24. WarbrickE, LaneDP, GloverDM, CoxLS (1995) A small peptide inhibitor of DNA replication defines the site of interaction between the cyclin-dependent kinase inhibitor p21WAF1 and proliferating cell nuclear antigen. Curr Biol 5: 275–282.

25. DerossiD, JoliotAH, ChassaingG, ProchiantzA (1994) The third helix of the Antennapedia homeodomain translocates through biological membranes. J Biol Chem 269: 10444–10450.

26. LeeJY, YuSJ, ParkYG, KimJ, SohnJ (2007) Glycogen synthase kinase 3beta phosphorylates p21WAF1/CIP1 for proteasomal degradation after UV irradiation. Mol Cell Biol 27: 3187–3198.

27. ChristensenJ, CotmoreSF, TattersallP (1997) A novel cellular site-specific DNA-binding protein cooperates with the viral NS1 polypeptide to initiate parvovirus DNA replication. J Virol 71: 1405–1416.

28. ChristensenJ, TattersallP (2002) Parvovirus initiator protein NS1 and RPA coordinate replication fork progression in a reconstituted DNA replication system. J Virol 76: 6518–6531.

29. AdeyemiRO, PintelDJ (2014) Parvovirus-induced depletion of cyclin b1 prevents mitotic entry of infected cells. PLoS Pathog 10: e1003891.

30. MoldovanGL, PfanderB, JentschS (2007) PCNA, the maestro of the replication fork. Cell 129: 665–679.

31. GartelAL, RadhakrishnanSK (2005) Lost in transcription: p21 repression, mechanisms, and consequences. Cancer Res 65: 3980–3985.

32. FunkJO, WagaS, HarryJB, EsplingE, StillmanB, et al. (1997) Inhibition of CDK activity and PCNA-dependent DNA replication by p21 is blocked by interaction with the HPV-16 E7 oncoprotein. Genes Dev 11: 2090–2100.

33. JonesDL, AlaniRM, MungerK (1997) The human papillomavirus E7 oncoprotein can uncouple cellular differentiation and proliferation in human keratinocytes by abrogating p21Cip1-mediated inhibition of cdk2. Genes Dev 11: 2101–2111.

34. GottweinE, CullenBR (2010) A human herpesvirus microRNA inhibits p21 expression and attenuates p21-mediated cell cycle arrest. J Virol 84: 5229–5237.

35. ChenH, LiC, HuangJ, CungT, SeissK, et al. (2011) CD4+ T cells from elite controllers resist HIV-1 infection by selective upregulation of p21. J Clin Invest 121: 1549–1560.

36. Saez-CirionA, HamimiC, BergamaschiA, DavidA, VersmisseP, et al. (2011) Restriction of HIV-1 replication in macrophages and CD4+ T cells from HIV controllers. Blood 118: 955–964.

37. AllouchA, DavidA, AmieSM, LahouassaH, ChartierL, et al. (2013) p21-mediated RNR2 repression restricts HIV-1 replication in macrophages by inhibiting dNTP biosynthesis pathway. Proc Natl Acad Sci U S A 110: E3997–4006 doi: 10.1073/pnas.1306719110

38. ChoiEY, NewmanAE, BurgerL, PintelD (2005) Replication of minute virus of mice DNA is critically dependent on accumulated levels of NS2. J Virol 79: 12375–12381.

39. NayakR, PintelDJ (2007) Positive and negative effects of adenovirus type 5 helper functions on adeno-associated virus type 5 (AAV5) protein accumulation govern AAV5 virus production. J Virol 81: 2205–2212.

40. MeerbreyKL, HuG, KesslerJD, RoartyK, LiMZ, et al. (2011) The pINDUCER lentiviral toolkit for inducible RNA interference in vitro and in vivo. Proc Natl Acad Sci U S A 108: 3665–3670.

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

Článok vyšiel v časopise

PLOS Pathogens


2014 Číslo 4
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Aktuální možnosti diagnostiky a léčby litiáz
nový kurz
Autori: MUDr. Tomáš Ürge, PhD.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#