Association of Cdk2/Cyclin E and NF-κB Complexes at G1/S Phase

Chen, Eying; Li, Chou-Chi H.

doi:10.1006/bbrc.1998.9224

Cited by 35 publications

(15 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These active complexes have the capacity to phosphorylate and partially inactivate the members of the retinoblastoma (RB) protein family including pRB and p107 [31]. Cyclin E is responsible for G1 to S phase progression by the CDK2-cyclin E complex [23,32]. We found that treatment with TH-39 could inhibit the activity of CDK2-cyclin E and CDK4/6-cyclin D complexes, consistent with the arrest of G0/G1 phase (Fig.5).…”

Section: Discussionsupporting

confidence: 52%

Small Molecule TH-39 Potentially Targets Hec1/Nek2 Interaction and Exhibits Antitumor Efficacy in K562 Cells via G0/G1 Cell Cycle Arrest and Apoptosis Induction

Zhu

Wei²,

Ye³

et al. 2016

Cell Physiol Biochem

View full text Add to dashboard Cite

Background: Cancer is still a major public health issue worldwide, and new therapeutics with anti-tumor activity are still urgently needed. Methods: The anti-tumor activity of TH-39, which shows potent anti-proliferative activity against K562 cells with an IC₅₀ of 0.78 µM, was investigated using immunoblot, co-immunoprecipitation, the MTT assay, and flow cytometry. Results: Mechanistically, TH-39 may disrupt the interaction between Hec1 and Nek2 in K562 cells. Moreover, TH-39 inhibited cell proliferation in a concentration- and time-dependent manner by influencing the morphology of K562 cells and inducing G0/G1 phase arrest. G0/G1 phase arrest was associated with down-regulation of CDK2-cyclin E complex and CDK4/6-cyclin D complex activities. Furthermore, TH-39 also induced cell apoptosis, which was associated with activation of caspase-3, down-regulation of Bcl-2 expression and up-regulation of Bax. TH-39 could also decrease mitochondrial membrane potential (Δψm) and increase reactive oxygen species (ROS) accumulation in K562 cells. The results indicated that TH-39 might induce apoptosis via the ROS-mitochondrial apoptotic pathway. Conclusion: This study highlights the potential therapeutic efficacy of the anti-cancer compound TH-39 in treatment-resistant chronic myeloid leukemia.

show abstract

Section: Discussionsupporting

confidence: 52%

Small Molecule TH-39 Potentially Targets Hec1/Nek2 Interaction and Exhibits Antitumor Efficacy in K562 Cells via G0/G1 Cell Cycle Arrest and Apoptosis Induction

Zhu

Wei²,

Ye³

et al. 2016

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…It also inactivates Smad3, a transcription factor that mediates the antiproliferative effects of the TGF-␤ receptor, via phosphorylation (51). CDK2 been shown to directly regulate the transcriptional activity of p300/CREB binding protein (52), as well as the RelA and c-Rel components of NF-B (52,53). Less is known about similar roles for CDK4 and CDK6, but there is evidence for cross-talk between NF-B and CDK4/6 pathways (54, 55).…”

Section: Discussionmentioning

confidence: 99%

The Cyclin-Dependent Kinase Inhibitor p27kip1 Is Required for Transplantation Tolerance Induced by Costimulatory Blockade

Rowell

Wang

Hancock

et al. 2006

The Journal of Immunology

View full text Add to dashboard Cite

The cyclin-dependent kinase (CDK) inhibitor p27kip1 is an important negative regulator of the cell cycle that sets a threshold for mitogenic signals in T lymphocytes, and is required for T cell anergy in vitro. To determine whether p27kip1 is required for tolerance in vivo, we performed cardiac allograft transplantation under conditions of combined CD28/CD40L costimulatory blockade. Although this treatment induced long-term allograft survival in wild-type recipients, costimulatory blockade was no longer sufficient to induce tolerance in mice lacking p27kip1. Rejected allografts from p27kip1−/− mice contained more CD4+ T lymphocytes and exhibited more tissue damage than allografts from tolerant, wild-type mice. Infiltrating p27kip1-deficient T cells, but not wild-type T cells, exhibited nuclear expression of cyclins E and A, indicating uncontrolled T cell cycle progression in the graft. The failure of tolerance in p27kip1−/− mice was also accompanied by markedly increased numbers of allospecific, IFN-γ-producing cells in the periphery, and occurred despite apparently normal regulatory T cell activity. These data demonstrate that the CDK inhibitor p27kip1 enforces the costimulatory requirement for the expansion and differentiation of alloimmune effector T lymphocytes in vivo, and point to CDKs as novel targets for immunosuppressive or tolerance-inducing therapies.

show abstract

“…266 Finally, p53 (the classic gatekeeper of cell cycle progression) and cyclin E-cdk2 may inhibit the antiapoptotic action of NF-B via the transcriptional co-activator protein CRB/p300. [267][268][269][270] Before NF-B binds to its promotor regions on DNA, it is acetylated by CRB/p300 which maintains its presence in the nucleus. P53 and cyclin E-cdk2 compete for the finite CRB/p300 complexes and prevent its interaction with NF-B.…”

Section: Spotlightmentioning

confidence: 99%

Nuclear transcription factor-κB as a target for cancer drug development

2002

View full text Add to dashboard Cite

Nuclear factor kappa B (NF-B) is a family of inducible transcription factors found virtually ubiquitously in all cells. Since its discovery by Sen and Baltimore in 1986, much has been discovered about its mechanisms of activation, its target genes, and its function in a variety of human diseases including those related to inflammation, asthma, atherosclerosis, AIDS, septic shock, arthritis, and cancer. Due to its role in a wide variety of diseases, NF-B has become one of the major targets for drug development. Here, we review our current knowledge of NF-B, the possible mechanisms of its activation, its potential role in cancer, and various strategies being employed to target the NF-B signaling pathway for cancer drug development.

show abstract

Association of Cdk2/Cyclin E and NF-κB Complexes at G1/S Phase

Cited by 35 publications

References 29 publications

Small Molecule TH-39 Potentially Targets Hec1/Nek2 Interaction and Exhibits Antitumor Efficacy in K562 Cells via G0/G1 Cell Cycle Arrest and Apoptosis Induction

Small Molecule TH-39 Potentially Targets Hec1/Nek2 Interaction and Exhibits Antitumor Efficacy in K562 Cells via G0/G1 Cell Cycle Arrest and Apoptosis Induction

The Cyclin-Dependent Kinase Inhibitor p27kip1 Is Required for Transplantation Tolerance Induced by Costimulatory Blockade

Nuclear transcription factor-κB as a target for cancer drug development

Contact Info

Product

Resources

About