NEDD8-targeting drug MLN4924 elicits DNA rereplication by stabilizing Cdt1 in S phase, triggering checkpoint activation, apoptosis, and senescence in cancer cells

Cancer Research

Volumn 70, Issue 24, 2010, Pages 10310-10320

  Lin, Jie Jessie ^a   Milhollen, Michael A ^b   Smith, Peter G ^b   Narayanan, Usha ^b   Dutta, Anindya ^a  

^a UNIVERSITY OF VIRGINIA   (United States)

^b MILLENNIUM PHARMACEUTICALS INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; CULLIN; CULLIN 1; CULLIN 2; CYCLIN DEPENDENT KINASE INHIBITOR 1; DNA; MLN 4924; NEDD8 PROTEIN; PROTEIN P53; REPLICATION LICENSING FACTOR CDT1; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CANCER CELL; CANCER CELL CULTURE; CELL AGING; CELL CYCLE S PHASE; CELL PROLIFERATION; COLORECTAL CANCER; CONTROLLED STUDY; DNA REPLICATION; DNA REREPLICATION; DRUG TARGETING; HUMAN; HUMAN CELL; HUMAN CELL CULTURE; PRIORITY JOURNAL; PROTEIN INDUCTION; PROTEIN STABILITY; SENESCENCE; WILD TYPE;

APOPTOSIS; CELL AGING; CELL CYCLE PROTEINS; COLORECTAL NEOPLASMS; CYCLIN-DEPENDENT KINASE INHIBITOR P21; CYCLOPENTANES; DNA REPLICATION; HCT116 CELLS; HUMANS; MOLECULAR TARGETED THERAPY; PYRIMIDINES; S PHASE; TUMOR SUPPRESSOR PROTEIN P53; UBIQUITIN-PROTEIN LIGASES; UBIQUITINS;

EID: 78650355357     PISSN: 00085472     EISSN: 15387445     Source Type: Journal    
DOI: 10.1158/0008-5472.CAN-10-2062     Document Type: Article

References (49)

1. Bell SP, Dutta A. DNA replication in eukaryotic cells. Annu Rev Biochem 2002;71:333-74.
2. Bell SP, Stillman B. ATP-dependent recognition of eukaryotic origins of DNA replication by a multiprotein complex. Nature 1992;357:128-34.
3. Dutta A, Bell SP. Initiation of DNA replication in eukaryotic cells. Annu Rev Cell Dev Biol 1997;13:293-332.
4. Lei M, Tye BK. Initiating DNA synthesis: from recruiting to activating the MCM complex. J Cell Sci 2001;114:1447-54.
5. Maiorano D, Moreau J, Mechali M. XCDT1 is required for the assembly of pre-replicative complexes in Xenopus laevis. Nature 2000;404:622-5.
6. Nishitani H, Lygerou Z, Nishimoto T, Nurse P. The Cdt1 protein is required to license DNA for replication in fission yeast. Nature 2000;404:625-8.
7. Arias EE, Walter JC. Strength in numbers: preventing rereplication via multiple mechanisms in eukaryotic cells. Genes Dev 2007;21:497-518.
8. Kim Y, Kipreos ET. Cdt1 degradation to prevent DNA re-replication: conserved and non-conserved pathways. Cell Div 2007;2:18.
9. Wohlschlegel JA, Dwyer BT, Dhar SK, Cvetic C, Walter JC, Dutta A. Inhibition of eukaryotic DNA replication by geminin binding to Cdt1. Science 2000;290:2309-12.
10. Tada S, Li A, Maiorano D, Mechali M, Blow JJ. Repression of origin assembly in metaphase depends on inhibition of RLF-B/Cdt1 by geminin. Nat Cell Biol 2001;3:107-13.
11. Machida YJ, Hamlin JL, Dutta A. Right place, right time, and only once: replication initiation in metazoans. Cell 2005;123:13-24.
12. Zhu W, Chen Y, Dutta A. Rereplication by depletion of geminin is seen regardless of p53 status and activates a G2/M checkpoint. Mol Cell Biol 2004;24:7140-50.
13. Jin J, Arias EE, Chen J, Harper JW, Walter JC. A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, which is required for S phase destruction of the replication factor Cdt1. Mol Cell 2006;23:709-21.
14. Zhong W, Feng H, Santiago FE, Kipreos ET. CUL-4 ubiquitin ligase maintains genome stability by restraining DNA-replication licensing. Nature 2003;423:885-9.
15. Gong L, Yeh ET. Identification of the activating and conjugating enzymes of the NEDD8 conjugation pathway. J Biol Chem 1999;274:12036-42.
16. Petroski MD, Deshaies RJ. Function and regulation of cullin-RING ubiquitin ligases. Nat Rev Mol Cell Biol 2005;6:9-20.
17. Read MA, Brownell JE, Gladysheva TB, et al. Nedd8 modification of cul-1 activates SCF(beta(TrCP))-dependent ubiquitination of Ikappa-Balpha. Mol Cell Biol 2000;20:2326-33.
18. Chiba T, Tanaka K. Cullin-based ubiquitin ligase and its control by NEDD8-conjugating system. Curr Protein Pept Sci 2004;5:177-84.
19. Petroski MD. Mechanism-based neddylation inhibitor. Chem Biol 2010;17:6-8.
20. Brownell JE, Sintchak MD, Gavin JM, et al. Substrate-assisted inhibition of ubiquitin-like protein-activating enzymes: the NEDD8 E1 inhibitor MLN4924 forms a NEDD8-AMP mimetic in situ. Mol Cell 2010;37:102-11.
21. Soucy TA, Smith PG, Milhollen MA, et al. An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer. Nature 2009;458:732-6.
22. Bunz F, Dutriaux A, Lengauer C, et al. Requirement for p53 and p21 to sustain G2 arrest after DNA damage. Science 1998;282:1497-501.
23. Abbas T, Sivaprasad U, Terai K, Amador V, Pagano M, Dutta A. PCNA-dependent regulation of p21 ubiquitylation and degradation via the CRL4Cdt2 ubiquitin ligase complex. Genes Dev 2008;22:2496-506.
24. Lin JJ, Dutta A. ATR pathway is the primary pathway for activating G2/M checkpoint induction after re-replication. J Biol Chem 2007;282:30357-62.
25. Montes de Oca R, Andreassen PR, Margossian SP, et al. Regulated interaction of the Fanconi anemia protein, FANCD2, with chromatin. Blood 2005;105:1003-9.
26. Zhu W DA. An ATR- and BRCA1-mediated Fanconi anemia pathway is required for activating the G2/M checkpoint and DNA damage repair upon rereplication. MCB 2006;26:4601-11
27. Dhar SK, Yoshida K, Machida Y, et al. Replication from oriP of Epstein-Barr virus requires human ORC and is inhibited by geminin. Cell 2001;106:287-96.
28. Sugimoto N, Tatsumi Y, Tsurumi T, et al. Cdt1 phosphorylation by cyclin A-dependent kinases negatively regulates its function without affecting geminin binding. J Biol Chem 2004;279:19691-7.
29. Takeda DY, Parvin JD, Dutta A. Degradation of Cdt1 during S phase is Skp2-independent and is required for efficient progression of mammalian cells through S phase. J Biol Chem 2005;280:23416-23.
30. Li X, Zhao Q, Liao R, Sun P, Wu X. The SCF(Skp2) ubiquitin ligase complex interacts with the human replication licensing factor Cdt1 and regulates Cdt1 degradation. J Biol Chem 2003;278:30854-8.
31. Hu J, McCall CM, Ohta T, Xiong Y. Targeted ubiquitination of CDT1 by the DDB1-CUL4A-ROC1 ligase in response to DNA damage. Nat Cell Biol 2004;6:1003-9.
32. Senga T, Sivaprasad U, Zhu W, et al. PCNA is a cofactor for Cdt1 degradation by CUL4/DDB1-mediated N-terminal ubiquitination. J Biol Chem 2006;281:6246-52.
33. Sansam CL, Shepard JL, Lai K, et al. DTL/CDT2 is essential for both CDT1 regulation and the early G2/M checkpoint. Genes Dev 2006;20:3117-29.
34. McGarry TJ. Geminin deficiency causes a Chk1-dependent G2 arrest in Xenopus. Mol Biol Cell 2002;13:3662-71.
35. Stein GH, Beeson M, Gordon L. Failure to phosphorylate the retinoblastoma gene product in senescent human fibroblasts. Science 1990;249:666-9.
36. Dimri GP, Lee X, Basile G, et al. A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci U S A 1995;92:9363-7.
37. Di Micco R, Fumagalli M, Cicalese A, et al. Oncogene-induced senescence is a DNA damage response triggered by DNA hyperreplication. Nature 2006;444:638-42.
38. Serrano M, Lin AW, McCurrach ME, Beach D, Lowe SW. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 1997;88:593-602.
39. Stein GH, Drullinger LF, Soulard A, Dulic V. Differential roles for cyclin-dependent kinase inhibitors p21 and p16 in the mechanisms of senescence and differentiation in human fibroblasts. Mol Cell Biol 1999;19:2109-17.
40. Zou X, Ray D, Aziyu A, et al. Cdk4 disruption renders primary mouse cells resistant to oncogenic transformation, leading to Arf/p53-independent senescence. Genes Dev 2002;16:2923-34.
41. Myohanen SK, Baylin SB, Herman JG. Hypermethylation can selectively silence individual p16ink4A alleles in neoplasia. Cancer Res 1998;58:591-3.
42. Han Z, Wei W, Dunaway S, et al. Role of p21 in apoptosis and senescence of human colon cancer cells treated with camptothecin. J Biol Chem 2002;277:17154-60.
43. Liontos M, Koutsami M, Sideridou M, et al. Deregulated overexpression of hCdt1 and hCdc6 promotes malignant behavior. Cancer Res 2007;67:10899-909.
44. Verschuren EW, Ban KH, Masek MA, Lehman NL, Jackson PK. Loss of Emi1-dependent anaphase-promoting complex/cyclosome inhibition deregulates E2F target expression and elicits DNA damage-induced senescence. Mol Cell Biol 2007;27:7955-65.
45. Alcorta DA, Xiong Y, Phelps D, Hannon G, Beach D, Barrett JC. Involvement of the cyclin-dependent kinase inhibitor p16 (INK4a) in replicative senescence of normal human fibroblasts. Proc Natl Acad Sci U S A 1996;93:13742-7.
46. Atadja P, Wong H, Garkavtsev I, Veillette C, Riabowol K. Increased activity of p53 in senescing fibroblasts. Proc Natl Acad Sci USA 1995;92:8348-52.
47. Brown JP, Wei W, Sedivy JM. Bypass of senescence after disruption of p21CIP1/WAF1 gene in normal diploid human fibroblasts. Science 1997;277:831-4.
48. Kang JY, Kim JJ, Jang SY, Bae YS. The p53-p21(Cip1/WAF1) pathway is necessary for cellular senescence induced by the inhibition of protein kinase CKII in human colon cancer cells. Mol Cells 2009;28:489-94.
49. Roninson IB, Broude EV, Chang BD. If not apoptosis, then what? Treatment-induced senescence and mitotic catastrophe in tumor cells. Drug Resist Updat 2001;4:303-13.