scholarly journals Upregulation of p27 cyclin-dependent kinase inhibitor and a C-terminus truncated form of p27 contributes to G1 phase arrest

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Takayuki Satoh ◽  
Daisuke Kaida
Keyword(s):  
Kinase Inhibitor ◽  
G1 Phase ◽  
Cyclin Dependent Kinase ◽  
Truncated Form ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Phase Arrest ◽  
C Terminus ◽  
G1 Phase Arrest

scholarly journals CCNE1 and E2F1 Partially Suppress G1 Phase Arrest Caused by Spliceostatin A Treatment

2021 ◽  
Vol 22 (21) ◽  
pp. 11623
Author(s):  
Kei Kikuchi ◽  
Daisuke Kaida
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Kinase Inhibitor ◽  
G1 Phase ◽  
Cell Cycle Regulators ◽  
Protein Levels ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Phase Arrest ◽  
G1 Phase Arrest ◽  
Spliceostatin A

The potent splicing inhibitor spliceostatin A (SSA) inhibits cell cycle progression at the G1 and G2/M phases. We previously reported that upregulation of the p27 cyclin-dependent kinase inhibitor encoded by CDKN1B and its C-terminal truncated form, namely p27*, which is translated from CDKN1B pre-mRNA, is one of the causes of G1 phase arrest caused by SSA treatment. However, the detailed molecular mechanism underlying G1 phase arrest caused by SSA treatment remains to be elucidated. In this study, we found that SSA treatment caused the downregulation of cell cycle regulators, including CCNE1, CCNE2, and E2F1, at both the mRNA and protein levels. We also found that transcription elongation of the genes was deficient in SSA-treated cells. The overexpression of CCNE1 and E2F1 in combination with CDKN1B knockout partially suppressed G1 phase arrest caused by SSA treatment. These results suggest that the downregulation of CCNE1 and E2F1 contribute to the G1 phase arrest induced by SSA treatment, although they do not exclude the involvement of other factors in SSA-induced G1 phase arrest.

Long Noncoding RNA GAS5 Targeting miR-221-3p/Cyclin-Dependent Kinase Inhibitor 2B Axis Regulates Follicular Thyroid Carcinoma Cell Cycle and Proliferation

Pathobiology ◽  
2021 ◽  
pp. 1-12
Author(s):  
Yuan Liu ◽  
Yi-Fang Li ◽  
Jia Liu ◽  
Zhi-Gang Deng ◽  
Li Zeng ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Thyroid Carcinoma ◽  
Noncoding Rna ◽  
Kinase Inhibitor ◽  
Follicular Thyroid Carcinoma ◽  
Cyclin Dependent Kinase ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Phase Arrest ◽  
G1 Phase Arrest

<b><i>Introduction:</i></b> Follicular thyroid carcinoma (FTC) is more aggressive than the most common papillary thyroid carcinoma (PTC). However, the current research on FTC is less than PTC. Here, we investigated the effects of long noncoding RNA (lncRNA) GAS5 and miR-221-3p in FTC. <b><i>Methods:</i></b> Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to detect GAS5 and miR-221-3p expression in the FTC tissues and cells. Cell proliferation was assessed by CCK8 and EdU assays. Flow cytometry was performed to determine the cell cycle. The dual-luciferase reporter assay was employed to validate the binding relationship of GAS5/miR-221-3p and miR-221-3p/cyclin-dependent kinase inhibitor 2B (CDKN2B). Western blot was conducted to measure the protein level of CDKN2B. <b><i>Results:</i></b> Our results displayed that GAS5 was downregulated, while miR-221-3p was upregulated in FTC tissues and cells. What’s more, overexpression of GAS5 or miR-221-3p inhibition induced G0/G1 phase arrest and inhibited cell proliferation of FTC cells. GAS5 acted as a sponge of miR-221-3p, and CDKN2B was a target gene of miR-221-3p. Additionally, GAS5 inhibited cell cycle and proliferation of FTC cells via reducing miR-221-3p expression to enhance CDKN2B expression. <b><i>Conclusion:</i></b> GAS5 induced G0/G1 phase arrest and inhibited cell proliferation via targeting miR-221-3p/CDKN2B axis in FTC. Thus, GAS5 may be a potential therapeutic target for the treatment of FTC.

Cyclic AMP-induced G1 phase arrest mediated by an inhibitor (p27Kip1) of cyclin-dependent kinase 4 activation

Cell ◽  
1994 ◽  
Vol 79 (3) ◽  
pp. 487-496 ◽  
Author(s):  
Jun-ya Kato ◽  
Masaaki Matsuoka ◽  
Kornelia Polyak ◽  
Joan Massague ◽  
Charles J. Sherr
Keyword(s):  
Cyclic Amp ◽  
G1 Phase ◽  
Cyclin Dependent Kinase ◽  
Phase Arrest ◽  
G1 Phase Arrest

G1 phase arrest by the phosphatidylinositol 3-kinase inhibitor LY 294002 is correlated to up-regulation of p27Kip1 and inhibition of G1 CDKs in choroidal melanoma cells

FEBS Letters ◽  
1998 ◽  
Vol 422 (3) ◽  
pp. 385-390 ◽  
Author(s):  
Fabrice Casagrande ◽  
Daniel Bacqueville ◽  
Marie-Jeanne Pillaire ◽  
François Malecaze ◽  
Stéphane Manenti ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Choroidal Melanoma ◽  
Melanoma Cells ◽  
G1 Phase ◽  
Phosphatidylinositol 3 Kinase ◽  
Phase Arrest ◽  
G1 Phase Arrest ◽  
Phosphatidylinositol 3

scholarly journals The Tumor Suppressor p53 and Histone Deacetylase 1 Are Antagonistic Regulators of the Cyclin-Dependent Kinase Inhibitor p21/WAF1/CIP1 Gene

2003 ◽  
Vol 23 (8) ◽  
pp. 2669-2679 ◽  
Author(s):  
Gerda Lagger ◽  
Angelika Doetzlhofer ◽  
Bernd Schuettengruber ◽  
Eva Haidweger ◽  
Elisabeth Simboeck ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Histone Deacetylase ◽  
Kinase Inhibitor ◽  
Genotoxic Stress ◽  
Cyclin Dependent Kinase ◽  
Tumor Suppressor P53 ◽  
Histone Deacetylase 1 ◽  
Cyclin Dependent Kinase Inhibitor ◽  
C Terminus ◽  
P21 Promoter

ABSTRACT The cyclin-dependent kinase inhibitor p21/WAF1/CIP1 is an important regulator of cell cycle progression, senescence, and differentiation. Genotoxic stress leads to activation of the tumor suppressor p53 and subsequently to induction of p21 expression. Here we show that the tumor suppressor p53 cooperates with the transcription factor Sp1 in the activation of the p21 promoter, whereas histone deacetylase 1 (HDAC1) counteracts p53-induced transcription from the p21 gene. The p53 protein binds directly to the C terminus of Sp1, a domain which was previously shown to be required for the interaction with HDAC1. Induction of p53 in response to DNA-damaging agents resulted in the formation of p53-Sp1 complexes and simultaneous dissociation of HDAC1 from the C terminus of Sp1. Chromatin immunoprecipitation experiments demonstrated the association of HDAC1 with the p21 gene in proliferating cells. Genotoxic stress led to recruitment of p53, reduced binding of HDAC1, and hyperacetylation of core histones at the p21 promoter. Our findings show that the deacetylase HDAC1 acts as an antagonist of the tumor suppressor p53 in the regulation of the cyclin-dependent kinase inhibitor p21 and provide a basis for understanding the function of histone deacetylase inhibitors as antitumor drugs.

scholarly journals Role of the UBL-UBA Protein KPC2 in Degradation of p27 at G1 Phase of the Cell Cycle

2005 ◽  
Vol 25 (21) ◽  
pp. 9292-9303 ◽  
Author(s):  
Taichi Hara ◽  
Takumi Kamura ◽  
Shuhei Kotoshiba ◽  
Hidehisa Takahashi ◽  
Kenichiro Fujiwara ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ubiquitin Ligase ◽  
Kinase Inhibitor ◽  
26S Proteasome ◽  
G1 Phase ◽  
Cyclin Dependent Kinase ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Uba Domain

ABSTRACT KPC2 (Kip1 ubiquitylation-promoting complex 2) together with KPC1 forms the ubiquitin ligase KPC, which regulates degradation of the cyclin-dependent kinase inhibitor p27 at the G1 phase of the cell cycle. KPC2 contains a ubiquitin-like (UBL) domain, two ubiquitin-associated (UBA) domains, and a heat shock chaperonin-binding (STI1) domain. We now show that KPC2 interacts with KPC1 through its UBL domain, with the 26S proteasome through its UBL and NH2-terminal UBA domains, and with polyubiquitylated proteins through its UBA domains. The association of KPC2 with KPC1 was found to stabilize KPC1 in a manner dependent on the STI1 domain of KPC2. KPC2 mutants that lacked either the NH2-terminal or the COOH-terminal UBA domain supported the polyubiquitylation of p27 in vitro, whereas a KPC2 derivative lacking the STI1 domain was greatly impaired in this regard. Depletion of KPC2 by RNA interference resulted in inhibition of p27 degradation at the G1 phase, and introduction of KPC2 derivatives into the KPC2-depleted cells revealed that the NH2-terminal UBA domain of KPC2 is essential for p27 degradation. These observations suggest that KPC2 cooperatively regulates p27 degradation with KPC1 and that the STI1 domain as well as the UBL and UBA domains of KPC2 are indispensable for its function.

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