Perspectives for cancer therapies with cdk2 inhibitors

Drug Resistance Updates

Volumn 4, Issue 6, 2001, Pages 347-367

  Wadler, Scott ^a  

^a WEILL CORNELL MEDICAL COLLEGE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

7 HYDROXYSTAUROSPORINE; CYCLIN DEPENDENT KINASE 2; CYCLIN DEPENDENT KINASE INHIBITOR; FLAVOPIRIDOL; RETINOBLASTOMA PROTEIN;

APOPTOSIS; CANCER CHEMOTHERAPY; CELL CYCLE G1 PHASE; CELL CYCLE G2 PHASE; CELL CYCLE S PHASE; CELL PROLIFERATION; CYTOSTASIS; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; REVIEW;

EID: 0035743983     PISSN: 13687646     EISSN: None     Source Type: Journal    
DOI: 10.1054/drup.2001.0224     Document Type: Review

References (201)

1. Complementation used to clone a human homologue of the fission yeast cell cycle control gene cdc2
2. A new human p34 protein kinase, CDK2, identified by complementation of a cdc28 mutation in Saccharomyces cerevisiae, is a homolog of Xenopus Egl
3. Cloning of a human cDNA encoding a CDC2-related kinase by complementation of a budding yeast cdc28 mutation
4. Characterization of the human cyclin-dependent kinase 2 gene. Promoter analysis and gene structure
5. Chromosomal mapping of human CDK2, CDK4, and CDK5 cell cycle kinase genes
6. Formation and activation of a cyclin E-Cdk2 complex during the G1 phase of the human cell cycle
7. Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex
8. Regulation of cyclin A-Cdk2 by SCF component Skp1 and F-box protein Skp2
9. Association of the cell cycle regulatory proteins p45(SKP2) and CksHs1. Functional effect on CDK2 complex formation and kinase activity
10. Crystal structure and mutational analysis of the human CDK2 kinase complex with cell cycle-regulatory protein CksHs1
11. A CDK-independent function of mammalian Cks1: Targeting of SCF(Skp2) to the CDK inhibitor p27Kip1
12. Kinetic basis for activation of CDK2/cyclin A by phosphorylation
13. The effects of changing the site of activating phosphorylation in CDK2 from threonine to serine
14. Differential regulation of Cdc2 and Cdk2 by RINGO and cyclins
15. Phosphorylation of the retinoblastoma protein by Cdk2
16. Cyclin E/Cdk2 and cyclin A/Cdk2 kinases associate with p107 and E2F in a temporally distinct manner
17. Association of Cdk2 kinase with the transcription factor E2F during S phase
18. Restoration of retinoblastoma mediated signaling to Cdk2 results in cell cycle arrest
19. p107 uses a p21CIP1-related domain to bind cyclin/Cdk2 and regulate interactions with E2F
20. A unique domain of pRb2/p130 acts as an inhibitor of Cdk2 kinase activity
21. Cdk2-dependent phosphorylation and functional inactivation of the pRB-related p130 protein in pRB(-), p16INK4A(+) tumor cells
22. A direct interaction between proliferating cell nuclear antigen (PCNA) and Cdk2 targets PCNA-interacting proteins for phosphorylation
23. Differential regulation of E2F transactivation by cyclin/Cdk2 complexes
24. Cyclin A/CDK2 binds directly to E2F-1 and inhibits the DNA-binding activity of E2F-1/DP-1 by phosphorylation
25. Phosphorylation of E2F-1 by cyclin A-Cdk2
26. Cyclin E-induced S phase without activation of the pRb/E2F pathway
27. Phosphorylation and activation of B-Myb by cyclin A-Cdk2
28. The cell-cycle regulated transcription factor B-Myb is phosphorylated by cyclin A/Cdk2 at sites that enhance its transactivation properties
29. Identification of cyclin A/Cdk2 phosphorylation sites in B-Myb
30. v-Jun overrides the mitogen dependence of S-phase entry by deregulating retinoblastoma protein phosphorylation and E2F-pocket protein interactions as a consequence of enhanced cyclin E-Cdk2 catalytic activity
31. A link between cell cycle and cell death: Bax and Bcl-2 modulate Cdk2 activation during thymocyte apoptosis
32. Cleavage of p21 Cip1/Waf1 and p27Kip1 mediates apoptosis in endothelial cells through activation of Cdk2: Role of a caspase cascade
33. Cdk2/cdc2 expression in colon carcinogenesis and effects of Cdk2/cdc2 inhibitor in colon cancer cells
34. Concurrent amplification of cyclin E and CDK2 genes in colorectal carcinomas
35. Coexpression of Cdk2/cdc2 and retinoblastoma gene products in colorectal cancer
36. Amplified CDK2 and cdc2 activities in primary colorectal carcinoma
37. Active cyclin A-CDK2 complex, a possible critical factor for cell proliferation in human primary lung carcinomas
38. Prognostic implications of cyclins (D1, E, A), cyclin-dependent kinases (CDK2, CDK4) and tumor-suppressor genes (pRB, p161INK4A) in childhood acute lymphoblastic leukemia
39. Analysis of cyclin E and CDK2 in ovarian cancer: Gene amplification and RNA overexpression
40. Overexpression of CDK2 is a prognostic indicator of oral cancer progression
41. A novel cyclin associates with MO 15/CDK7 to form the CDK-activating kinase
42. Function of a human cyclin gene as an oncogene
43. Cyclin D1 transgene impedes lymphocyte maturation and collaborates in lymphomagenesis with the myc gene
44. Overexpression of mouse D-type cyclins accelerates G1 phase in rodent fibroblasts
45. Analysis of cell cycle-related gene expression in postmitotic neurons: Selective induction of Cyclin D1 during programmed cell death
46. Cyclin D1 is an essential mediator of apoptotic neuronal cell death
47. Deregulation of cyclins D1 and E and suppression of Cdk2 and Cdk4 in senescent human fibroblasts
48. Altered regulation of G1 cyclins in senescent human diploid fibroblasts: Accumulation of inactive cyclin E-Cdk2 and cyclin D1-Cdk2 complexes
49. Inducible expression of cyclin D1 in T-47D human breast cancer cells is sufficient for Cdk2 activation and pRB hyperphosphorylation
50. Cyclin D1-mediated inhibition of repair and replicative DNA synthesis in human fibroblasts
51. Increased expression of cyclin D1 in a murine mammary epithelial cell line induces p271kip1, inhibits growth, and enhances apoptosis
52. Cyclin D1 inhibits cell proliferation through binding to PCNA and Cdk2
53. Association of human cyclin E with a periodic G-S phase protein kinase
54. Requirement of cyclin E-Cdk2 inhibition in p16(INK4a)-mediated growth suppression
55. Functional inactivation of the retinoblastoma protein requires sequential modification by at least two distinct cyclin-Cdk complexes
56. E2F-1 accumulation bypasses a G1 arrest resulting from the inhibition of G1 cyclin-dependent kinase activity
57. Cdk2-dependent and-independent pathways in E2F-mediated S phase induction
58. Expression of NPAT, a novel substrate of cyclin E-CDK2, promotes S-phase entry
59. Histone acetylation and the cell-cycle in cancer
60. Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription
61. NPAT links cyclin E-Cdk2 to the regulation of replication-dependent histone gene transcription
62. Transcription factor E2F and cyclin E-Cdk2 complex cooperate to induce chromosomal DNA replication in Xenopus oocytes
63. Cyclin A is required for the onset of DNA replication in mammalian fibroblasts
64. Cyclin A is required in S phase in normal epithelial cells
65. The Cdk2 kinase is required for the G-to-S transition in mammalian cells
66. Human cyclin E, a nuclear protein essential for the G-to-S phase transition
67. Acceleration of the G/S phase transition by expression of cyclins Dand E with an inducible system
68. Cyclin A-associated kinase activity is rate limiting for entrance into S phase and is negatively regulated in G1 by p27Kip1
69. Cyclin/Cdk-dependent initiation of DNA replication in a human cell-free system
70. Cell cycle control of DNA replication
71. Loading of an Mcm protein onto DNA replication origins is regulated by Cdc6p and CDKs
72. Cdc6p-dependent loading of Mcm proteins onto pre-replicative chromatin in budding yeast
73. The Xenopus Cdc6 protein is essential for the initiation of a single round of DNA replication in cell-free extracts
74. Components and dynamics of DNA replication complexes in S. cerevisiae: Redistribution of MCM proteins and Cdc45p during S phase
75. ORC and Cdc6p interact and determine the frequency of initiation of DNA replication in the genome
76. Cdc6p modulates the structure and DNA binding activity of the origin recognition complex in vitro
77. A role for Cdk2 kinase in negatively regulating DNA replication during S phase of the cell cycle
78. Identification of a preinitiation step in DNA replication that is independent of origin recognition complex and cdc6, but dependent on Cdk2
79. Multistep regulation of DNA replication by Cdk phosphorylation of HsCdc6
80. Human CDC6/Cdc18 associates with Orc1 and cyclin-Cdk and is selectively eliminated from the nucleus at the onset of S phase
81. Mutation of cyclin/Cdk phosphorylation sites in HsCdc6 disrupts a late step in initiation of DNA replication in human cells
82. Triggering ubiquitination of a CDK inhibitor at origins of DNA replication
83. Cyclin-dependent kinase control of centrosome duplication
84. Cyclin-dependent kinase 2 (Cdk2) is required for centrosome duplication in mammalian cells
85. Requirement of Cdk2-cyclin E activity for repeated centrosome reproduction in Xenopus egg extracts
86. Specific phosphorylation of nucleophosmin on Thr(199) by cyclin-dependent kinase 2-cyclin E and its role in centrosome duplication
87. Nucleophosmin/B23 is a target of CDK2/cyclin E in centrosome duplication
88. Requirement of Cyclin/Cdk2 and protein phosphatase I activity for chromatin assembly factor 1 -dependent chromatin assembly during DNA synthesis
89. S and G2 phase roles for Cdk2 revealed by inducible expression of a dominant-negative mutant in human cells
90. Cdc25-dependent activation of cyclin A/Cdk2 is blocked in G2 phase arrested cells independently of ATM/ATR
91. Human p55(CDC)/Cdc20 associates with cyclin A and is phosphorylated by the cyclin A-Cdk2 complex
92. A conserved cyclinbinding domain determines functional interplay between anaphase-promoting complex-Cdh1 and cyclin A-Cdk2 during cell cycle progression
93. The adenovirus E1A-associated kinase consists of cyclin E-p33Cdk2 and cyclin A-p33Cdk2
94. A novel function of adenovirus E1A is required to overcome growth arrest by the CDK2 inhibitor p27(Kip1)
95. Human papillomavirus E7 oncoproteins bind a single form of cyclin E in a complex with Cdk2 and p107
96. The human papillomavirus E7 oncoprotein can uncouple cellular differentiation and proliferation in human keratinocytes by abrogating p21Cip1-mediated inhibition of Cdk2
97. Initiation of DNA synthesis by human papillomavirus E7 oncoproteins is resistant to p21-mediated inhibition of cyclin E-Cdk2 activity
98. Functional interaction between the bovine papillomavirus virus type 1 replicative helicase E1 and cyclin E-Cdk2
99. Human cytomegalovirus infection results in altered Cdk2 subcellular localization
100. Inhibition of Cellular Cdk2 activity blocks human cytomegalovirus replication
101. Functional interactions between herpesvirus oncoprotein MEQ and cell cycle regulator CDK2
102. Association of cyclin A and Cdk2 with SV40 DNA in replication initiation complexes is cell cycle dependent
103. Inhibition of CDK2 activity in vivo by an associated 20K regulatory subunit
104. Structural studies of p21Waf1/Cip1/Sdi1 in the free and Cdk2-bound state: Conformational disorder mediates binding diversity
105. The amino terminus of Cdk2 binds p21
106. p21 contains independent binding sites for cyclin and Cdk2: Both sites are required to inhibit Cdk2 kinase activity
107. p21(Waf1/Cip1) inhibition of cyclin E/Cdk2 activity prevents endoreduplication after mitotic spindle disruption
108. The Cdk2 binding domain of p27Kip correlates with the inhibition of the kinase activity of Cdk2/cyclin complexes
109. Differential interaction of the cyclin-dependent kinase (Cdk) inhibitor p27Kip1 with cyclin A-Cdk2 and cyclin D2-Cdk4
110. A new pathway for mitogen-dependent Cdk2 regulation uncovered in p27(Kip1)-deficient cells
111. Cyclin E-CDK2 is a regulator of p27Kip1
112. Identification of Cdk2 binding sites on the p27Kip1 cyclin-dependent kinase inhibitor
113. The N-terminal domains of cyclin-dependent kinase inhibitory proteins block the phosphorylation of Cdk2/Cyclin E by the CDK-activating kinase
114. The INK4 family of cell cycle inhibitors in cancer
115. Mechanisms of cyclin-dependent kinase regulation: Structures of Cdks, their cyclin activators, and Cip and INK4 inhibitors
116. Induced expression of p16(INK4a) inhibits both CDK4- and CDK2-associated kinase activity by reassortment of cyclin-CDK-inhibitor complexes
117. Induction of p21(WAF1/CIP1) and inhibition of Cdk2 mediated by the tumor suppressor p16(INK4a)
118. The subcellular locations of p15(Ink4b) and p27(Kip1) coordinate their inhibitory interactions with Cdk4 and Cdk2
119. Cellular factors may enable squamous carcinoma cells to overcome TGF beta-mediated repression of CDK2 activity
120. Caspase-mediated Cdk2 activation is a critical step to execute transforming growth factor-beta 1-induced apoptosis in human gastric cancer cells
121. Myc and Ras collaborate in inducing accumulation of active cyclin E/Cdk2 and E2F
122. Repression of c-Myc responsive genes in cyclin cells causes G1 arrest through reduction of cyclin E/CDK2 kinase activity
123. Cdk2-dependent phosphorylation of p27 facilitates its Myc-induced release from cyclin E/Cdk2 complexes
124. Myc activation of cyclin E/Cdk2 kinase involves induction of cyclin E gene transcription and inhibition of p27(Kip1) binding to newly formed complexes
125. Cyclin A and Cdk2 kinase activity are suppressed by combined treatment with tumor necrosis factor-alpha and interferon-alpha
126. Nitric oxide-induced downregulation of Cdk2 activity and cyclin A gene transcription in vascular smooth muscle cells
127. PKCeta associates with cyclin E/Cdk2/p21 complex, phosphorylates p21 and inhibits Cdk2 kinase in keratinocytes
128. Characterization of Cdk2-cyclin E complexes in plasma membrane and endosomes of liver parenchyma. Insulin-dependent regulation
129. Regulation of Cdk2 activity in endothelial cells that are inhibited from growth by cell contact
130. Estrogen-dependent cyclin E-Cdk2 activation through p21 redistribution
131. Estrogen-induced activation of Cdk4 and Cdk2 during G-S phase progression is accompanied by increased cyclin D1 expression and decreased cyclin-dependent kinase inhibitor association with cyclin E-Cdk2
132. Progesterone inhibits estrogen-induced cyclin D1 and Cdk4 nuclear translocation, cyclin E- and cyclin A-Cdk2 kinase activation, and cell proliferation in uterine epithelial cells in mice
133. A pure estrogen antagonist inhibits cyclin E-Cdk2 activity in MCF-7 breast cancer cells and induces accumulation of p130-E2F4 complexes characteristic of quiescence
134. Regulation of estrogen receptor transcriptional enhancement by the cyclin A/Cdk2 complex
135. c-Myc or cyclin D1 mimics estrogen effects on cyclin E-Cdk2 activation and cell cycle reentry
136. Insulin/insulin-like growth factor-1 and estrogen cooperate to stimulate cyclin E-Cdk2 activation and cell Cycle progression in MCF-7 breast cancer cells through differential regulation of cyclin E and p21 (WAF1/Cip1)
137. Regulation of androgen-dependent prostatic cancer cell growth: Androgen regulation of CDK2, CDK4, and CKI p16 genes
138. Flavopiridol: The first cyclin-dependent kinase inhibitor in human clinical trials
139. Flavopiridol induces G1 arrest with inhibition of cyclin-dependent kinase (CDK) 2 and CDK4 in human breast carcinoma cells
140. Flavopiridol, a cyclin-dependent kinase inhibitor, prevents spindle inhibitor-induced endoreduplication in human cancer cells
141. Bcl-2 independence of flavopiridol-induced apoptosis. Mitochondrial depolarization in the absence of cytochrome c release
142. Overexpression of the ATP-binding cassette half-transporter, ABCG2 (MXR/BCRP/ABCPI), in flavopiridol-resistant human breast cancer cells
143. Cytotoxic synergy between flavopiridol (NSC 649890, L86-8275) and various antineoplastic agents: The importance of sequence of administration
144. Flavopiridol increases sensitization to gemcitabine in human gastrointestinal cancer cell lines and correlates with down-regulation of ribonucleotide reductase M2 subunit
145. Sequential dependent enhancement of caspase activation and apoptosis by flavopiridol on paclitaxel-treated human gastric and breast cancer cells
146. Flavopiridol, a novel cyclin-dependent kinase inhibitor, in metastatic renal cancer: A University of Chicago Phase II Consortium study
147. Phase II study of the cyclin-dependent kinase inhibitor flavopiridol administered to patients with advanced gastric carcinoma
148. Structural basis for specificity and potency of a flavonoid inhibitor of human CDK2, a cell cycle kinase
149. Effects of structurally related flavonoids on cell cycle progression of human melanoma cells: Regulation of cyclin-dependent kinases CDK2 and CDK1
150. G1 phase accumulation induced by UCN-01 is associated with dephosphorylation of Rb and CDK2 proteins as well as induction of CDK inhibitor p21/Cip1/WAF1/Sdi1 in p53-mutated human epidermoid carcinoma A431 cells
151. UCN-01: A potent abrogator of G2 checkpoint function in cancer cells with disrupted p53
152. UCN-01 suppresses E2F-1 mediated by ubiquitin-proteasome-dependent degradation
153. Interactions between 2-fluoroadenine 9-beta-D-arabinofuranoside and the kinase inhibitor UCN-01 in human leukemia and lymphoma cells
154. Enhancement of cisplatin-induced cytotoxicity by 7-hydroxystaurosporine (UCN-01), a new G2-checkpoint inhibitor
155. Phase 1 trial of 72-hour continuous infusion UCN-01 in patients with refractory neoplasms
156. Both low and high concentrations of staurosporine induce G1 arrest through down-regulation of cyclin E and Cdk2 expression
157. Treatment of human glioblastoma cells with the staurosporine derivative CGP 41251 inhibits CDC2 and CDK2 kinase activity and increases radiation sensitivity
158. Inhibition of cyclin-dependent kinases by purine analogues: Crystal structure of human Cdk2 complexed with roscovitine
159. Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, Cdk2 and Cdk5
160. CVT-313, a specific and potent inhibitor of CDK2 that prevents neointimal proliferation
161. Olomoucine, an inhibitor of the cdc2/Cdk2 kinases activity, blocks plant cells at the G1 to S and G2 to M cell cycle transitions
162. Cyclin-Dependent Kinase Inhibition by New C-2 Alkynylated Purine Derivatives and Moleculare Structure of a CDK2-Inhibitor Complex
163. The tryphostin AG17 induces apoptosis and inhibition of Cdk2 activity in a lymphoma cell line that overexpresses bcl-2
164. Tyrphostin AG 494 blocks Cdk2 activation
165. Inhibition of Cdk2 activation by selected tyrphostins causes cell cycle arrest at late G1 and S phase
166. CDK2 is a target for retinoic acid-mediated growth inhibition in MCF-7 human breast cancer cells
167. Lycopene inhibition of cell cycle progression in breast and endometrial cancer cells is associated with reduction in cyclin D levels and retention of p27(Kip1) in the cyclin E-Cdk2 complexes
168. Retinoblastoma protein-overexpressing HL60 cells resistant to 1,25-dihydroxyvitamin D3 display increased CDK2 and CDK6 activity and shortened G1 phase
169. A vitamin D3 analog induces a G1-phase arrest in CaCo-2 cells by inhibiting Cdk2 and Cdk6: Roles of cyclin E, p21 Waf1, and p27Kip1
170. Inhibition of Cdk2 kinase activity by methylselenocysteine in synchronized mouse mammary epithelial tumor cells
171. Lovastatin mediated G1 arrest in normal and tumor breast cells is through inhibition of CDK2 activity and redistribution of p21 and p27, independent of p53
172. Eicosapentaenoic acid and docosahexaenoic acid inhibit vascular smooth muscle cell proliferation by inhibiting phosphorylation of Cdk2-cyclinE complex
173. G1 phase-specific suppression of the Cdk2 activity by ginsenoside Rh2 in cultured murine cells
174. Suppression of neointimal smooth muscle cell accumulation in vivo by antisense cdc2 and Cdk2 oligonucleotides in rat carotid artery
175. Inhibition of the melanoma cell cycle and regulation at the G/S transition by 12-O-tetradecanoylphorbol-13-acetate (TPA) by modulation of CDK2 activity
176. Hyperoxia induces S-phase cell-cycle arrest and p21 (Cip1/Waf1)-independent Cdk2 inhibition in human carcinoma T47D-H3 cells
177. Prevention of chemotherapy-induced alopecia in rats by CDK inhibitors
178. Selective killing of transformed cells by cyclin/cyclin-dependent kinase 2 antagonists
179. A novel Cdk2-selective inhibitor, SU9516, induces apoptosis in colon carcinoma cells
180. The Cdk2/cyclinA inhibitor Pnu-252808 blocks cell cycle progression and induces apoptosis in tumor cells both in vitro and in vivo
181. Aminothiazole inhibitors of cyclin dependent kinase 2 block cell cycle progression and induce apoptosis
182. Discovery and development of 2-amino-5-tioalkylaryl thiazoles as inhibitors of cyclin dependent kinase 2
183. Structure-based design of potent inhibitors of Cdk1 and Cdk2
184. Hepatitis B virus integration in a cyclin A gene in a hepatocellular carcinoma
185. Isolation of three novel human cyclins by rescue of G1 cyclin (Cn) function in yeast
186. The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases
187. p27, a novel inhibitor of G1 cyclin-Cdk protein kinase activity, is related to p21
188. Synthesis of the nuclear protein cyclin (PCNA) and its relationship with DNA replication
189. p19Skp1 and p45Skp2 are essential elements of the cyclin A-CDK2 S phase Kinase
190. SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box
191. Human cDNAs encoding homologs of the small p34Cdc28/Cdc2-associated protein of Saccharomyces cerevisiae and Schizosaccharomyces pombe
192. Complete genomic sequence of the human retinoblastoma susceptibility gene
193. Genomic structure of the human retinoblastoma-related Rb2/p130 gene
194. Molecular cloning, chromosomal mapping, and expression of the cDNA for p107, a retinoblastoma gene product-related protein
195. Adenovirus E1A proteins can dissociate heteromeric complexes involving the E2F transcription factor: A novel mechanism for E1A trans-activation
196. The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53
197. T antigen is bound to a host protein in SV40-transformed cells
198. The 72K IE1 and 80K IE2 proteins of human cytomegalovirus independently trans-activate the c-fos, c-myc and hsp70 promoters via basal promoter elements
199. Cytomegalovirus infection induces high levels of cyclins, phosphorylated Rb, and p53, leading to cell cycle arrest
200. The relevance of drug sequence in combination chemotherapy
201. Cyclin-dependent kinases inhibitors as potential anticancer, antineurodegenerative, antiviral and antiparasitic agents