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Positively charged residues located downstream of PIP box, together with TD amino acids within PIP box, are important for CRL4(Cdt2) -mediated proteolysis.

Michishita M, Morimoto A, Ishii T, Komori H, Shiomi Y, Higuchi Y, Nishitani H.

Genes Cells. 2011 Jan;16(1):12-22. doi: 10.1111/j.1365-2443.2010.01464.x. Epub 2010 Dec 9.


Docking of a specialized PIP Box onto chromatin-bound PCNA creates a degron for the ubiquitin ligase CRL4Cdt2.

Havens CG, Walter JC.

Mol Cell. 2009 Jul 10;35(1):93-104. doi: 10.1016/j.molcel.2009.05.012.


CRL4Cdt2 E3 ubiquitin ligase and proliferating cell nuclear antigen (PCNA) cooperate to degrade thymine DNA glycosylase in S phase.

Shibata E, Dar A, Dutta A.

J Biol Chem. 2014 Aug 15;289(33):23056-64. doi: 10.1074/jbc.M114.574210. Epub 2014 Jun 24.


Direct role for proliferating cell nuclear antigen in substrate recognition by the E3 ubiquitin ligase CRL4Cdt2.

Havens CG, Shobnam N, Guarino E, Centore RC, Zou L, Kearsey SE, Walter JC.

J Biol Chem. 2012 Mar 30;287(14):11410-21. doi: 10.1074/jbc.M111.337683. Epub 2012 Feb 2.


The CRL4Cdt2 ubiquitin ligase mediates the proteolysis of cyclin-dependent kinase inhibitor Xic1 through a direct association with PCNA.

Kim DH, Budhavarapu VN, Herrera CR, Nam HW, Kim YS, Yew PR.

Mol Cell Biol. 2010 Sep;30(17):4120-33. doi: 10.1128/MCB.01135-09. Epub 2010 Jul 6.


PCNA-dependent ubiquitination of Cdt1 and p21 in mammalian cells.

Hayashi A, Suenaga N, Shiomi Y, Nishitani H.

Methods Mol Biol. 2014;1170:367-82. doi: 10.1007/978-1-4939-0888-2_19.


PIP degron proteins, substrates of CRL4Cdt2, and not PIP boxes, interfere with DNA polymerase η and κ focus formation on UV damage.

Tsanov N, Kermi C, Coulombe P, Van der Laan S, Hodroj D, Maiorano D.

Nucleic Acids Res. 2014 Apr;42(6):3692-706. doi: 10.1093/nar/gkt1400. Epub 2014 Jan 14.


Thymine DNA glycosylase is a CRL4Cdt2 substrate.

Slenn TJ, Morris B, Havens CG, Freeman RM Jr, Takahashi TS, Walter JC.

J Biol Chem. 2014 Aug 15;289(33):23043-55. doi: 10.1074/jbc.M114.574194. Epub 2014 Jun 19.


Two different replication factor C proteins, Ctf18 and RFC1, separately control PCNA-CRL4Cdt2-mediated Cdt1 proteolysis during S phase and following UV irradiation.

Shiomi Y, Hayashi A, Ishii T, Shinmyozu K, Nakayama J, Sugasawa K, Nishitani H.

Mol Cell Biol. 2012 Jun;32(12):2279-88. doi: 10.1128/MCB.06506-11. Epub 2012 Apr 9.


CDK1-dependent inhibition of the E3 ubiquitin ligase CRL4CDT2 ensures robust transition from S Phase to Mitosis.

Rizzardi LF, Coleman KE, Varma D, Matson JP, Oh S, Cook JG.

J Biol Chem. 2015 Jan 2;290(1):556-67. doi: 10.1074/jbc.M114.614701. Epub 2014 Nov 19.


Sequential replication-coupled destruction at G1/S ensures genome stability.

Coleman KE, Grant GD, Haggerty RA, Brantley K, Shibata E, Workman BD, Dutta A, Varma D, Purvis JE, Cook JG.

Genes Dev. 2015 Aug 15;29(16):1734-46. doi: 10.1101/gad.263731.115. Epub 2015 Aug 13.


PCNA-coupled p21 degradation after DNA damage: The exception that confirms the rule?

Soria G, Gottifredi V.

DNA Repair (Amst). 2010 Apr 4;9(4):358-64. doi: 10.1016/j.dnarep.2009.12.003. Epub 2010 Jan 8. Review.


Proliferating cell nuclear antigen-dependent rapid recruitment of Cdt1 and CRL4Cdt2 at DNA-damaged sites after UV irradiation in HeLa cells.

Ishii T, Shiomi Y, Takami T, Murakami Y, Ohnishi N, Nishitani H.

J Biol Chem. 2010 Dec 31;285(53):41993-2000. doi: 10.1074/jbc.M110.161661. Epub 2010 Oct 7.


Cell type-dependent requirement for PIP box-regulated Cdt1 destruction during S phase.

Lee HO, Zacharek SJ, Xiong Y, Duronio RJ.

Mol Biol Cell. 2010 Nov 1;21(21):3639-53. doi: 10.1091/mbc.E10-02-0130. Epub 2010 Sep 8.


PCNA-dependent regulation of p21 ubiquitylation and degradation via the CRL4Cdt2 ubiquitin ligase complex.

Abbas T, Sivaprasad U, Terai K, Amador V, Pagano M, Dutta A.

Genes Dev. 2008 Sep 15;22(18):2496-506. doi: 10.1101/gad.1676108.


The helicase FBH1 is tightly regulated by PCNA via CRL4(Cdt2)-mediated proteolysis in human cells.

Bacquin A, Pouvelle C, Siaud N, Perderiset M, Salomé-Desnoulez S, Tellier-Lebegue C, Lopez B, Charbonnier JB, Kannouche PL.

Nucleic Acids Res. 2013 Jul;41(13):6501-13. doi: 10.1093/nar/gkt397. Epub 2013 May 15.


CRL4(CDT2) targets CHK1 for PCNA-independent destruction.

Huh J, Piwnica-Worms H.

Mol Cell Biol. 2013 Jan;33(2):213-26. doi: 10.1128/MCB.00847-12. Epub 2012 Oct 29.


A novel function of CRL4(Cdt2): regulation of the subunit structure of DNA polymerase δ in response to DNA damage and during the S phase.

Zhang S, Zhao H, Darzynkiewicz Z, Zhou P, Zhang Z, Lee EY, Lee MY.

J Biol Chem. 2013 Oct 11;288(41):29550-61. doi: 10.1074/jbc.M113.490466. Epub 2013 Aug 2.


CRL4(Cdt2) E3 ubiquitin ligase monoubiquitinates PCNA to promote translesion DNA synthesis.

Terai K, Abbas T, Jazaeri AA, Dutta A.

Mol Cell. 2010 Jan 15;37(1):143-9. doi: 10.1016/j.molcel.2009.12.018.

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