1.Expression and clinical significance of cyclin H and CDK7 in human hemangiomas.
Juan LIU ; Duan-Lian ZHANG ; Sheng-Guo SHAN
Chinese Journal of Plastic Surgery 2008;24(4):300-302
OBJECTIVETo investigate the expression and clinical significance of cyclin H and cyclin-dependent kinase 7 (CDK7) in human hemangiomas.
METHODSImmunohistochemistry technique was used to measure the expression of cyclin H and CDK7 proteins in proliferative, involuting hemangiomas and normal skin tissues. Immunohistochemical technique for factor VIII-related antigen was used to prove that the cells which expressed cyclin H and CDK7 were endothelial cells. Average optical density and positive area of the expression of cyclin H and CDK7 proteins in proliferative, involuting hemangiomas and normal skin tissues were measured by image analysis (HPIAS-1000).
RESULTSThe expression of cyclin H and CDK7 protein in proliferating hemangiomas was significantly higher than that in involuting hemangiomas and normal skin tissues (P < 0.01). But no significant difference was found in the expression of cyclin H and CDK7 protein between involuting hemangiomas and normal skin tissues (P > 0.05).
CONCLUSIONScyclin H and CDK7 may play an important role in the generation and development of human hemangiomas.
Cyclin H ; metabolism ; Cyclin-Dependent Kinases ; metabolism ; Hemangioma ; metabolism ; Humans ; Immunohistochemistry ; Skin Neoplasms ; metabolism
2.Expression of p27Kip1 Protein Associated with Poor Clinical Outcome in Human Gastric Cancer.
Dong Su BU ; Se Hwan HAN ; Byung Noe BAE ; Ki Hwan KIM ; Hong Joo KIM ; Young Duck KIM ; Hong Yong KIM ; Kyeong Mee PARK
Journal of the Korean Surgical Society 2001;61(2):153-157
PURPOSE: p27Kip1 protein is an inhibitor of cyclin-dependent kinases and is thought to be a potential prognostic indicator for numerous human cancers. We investigated the expression of p27Kip1 in gastric cancer in order to estimate its clinical utility. METHODS: Immunohistochemical assay for p27Kip1 protein was performed in 64 patients with primary gastric cancer. The correlation between p27Kip1 and clinical-biological parameters including patient survival was analyzed. RESULTS: p27Kip1 expression was suppressed in 40 (62.5%) of 64 gastric cancer patients. Expression of p27Kip1 was significantly reduced in poorly differentiated cancers (82.1%, 23/28; P=0.015) and was also reduced in tumors with a high S-phase fraction as compared with tumors showing a low S-phase fraction (86.7%, 26/30, 41.2%, 14/34; P=0.0002). In univariate analysis, the extent of the disease (P<0.001), and reduced expression of p27Kip1 (P=0.0006) were statistically significant to predict the patient's outcome, however depth of invasion (P=0.008) and pathologic stage (P=0.009) emerged as significant prognostic indicators in the multivariate analysis. CONCLUSION: The expression of p27Kip1 is closely linked with cell proliferation and differentiation of human gastric cancer. p27Kip1 appears to have potential as a prognostic marker in the management of gastric cancer patients.
Cell Proliferation
;
Cyclin-Dependent Kinase Inhibitor p27*
;
Cyclin-Dependent Kinases
;
Humans*
;
Immunohistochemistry
;
Multivariate Analysis
;
Prognosis
;
Stomach Neoplasms*
3.Expressions of cyclin E, cyclin dependent kinase 2 and p57(KIP2) in human gastric cancer.
Bin LIANG ; Shan WANG ; Xiaodong YANG ; Yingjiang YE ; Yongxiang YU ; Zhirong CUI
Chinese Medical Journal 2003;116(1):20-23
OBJECTIVETo investigate the expressions of cyclin E, cyclin dependent kinase 2 (CDK-2) and cyclin-dependent kinase inhibitor p57(KIP2) in human gastric cancer, and to evaluate the relationships between protein levels and clinicopathological parameters.
METHODSWestern blot was used to measure the expressions of cyclin E, CDK-2 and p57(KIP2) proteins in the surgically resected gastric carcinoma, adjacent normal mucosa and metastatic lymph nodes from 36 patients.
RESULTSCyclin E and CDK-2 protein levels were higher in gastric cancer tissues in comparison with normal tissues (P < 0.05). Overexpression of cyclin E was correlated with lymph node involvement, poor histological grade and serosa invasion (P < 0.05). Overexpression of CDK-2 was correlated with lymph nodes involvement (P < 0.05). No statistically significant difference between cyclin E and CDK-2 expression was found when samples were stratified according to tumor size (P > 0.05). Expression of cyclin E and CDK-2 showed a positive linear correlation (r = 0.451, P = 0.01). Protein levels of p57(KIP2) were lower in gastric cancer tissues than in the normal mucosa (P < 0.05). Decreased expression of p57(KIP2) was correlated with lymph node involvement (P < 0.05). No statistically significant difference in p57(KIP2) expression was found when sample were stratified according to tumor size, histological grade or serosa invasion (P > 0.05). In metastatic lymph nodes, expression of cyclin E was increased and the expression of p57(KIP2) decreased.
CONCLUSIONOverexpressions of cyclin E, CDK-2 and downregulated expression of p57(KIP2) may play important roles in tumorigenesis and metastatic potential of gastric cancer.
Blotting, Western ; CDC2-CDC28 Kinases ; Cyclin E ; analysis ; physiology ; Cyclin-Dependent Kinase 2 ; Cyclin-Dependent Kinase Inhibitor p57 ; Cyclin-Dependent Kinases ; analysis ; physiology ; Humans ; Lymphatic Metastasis ; Nuclear Proteins ; analysis ; physiology ; Protein-Serine-Threonine Kinases ; analysis ; physiology ; Stomach Neoplasms ; chemistry ; pathology
4.Effects of Erk signal transduction on the cell cycle of rat hepatic stellate cells stimulated by acetaldehyde.
Ming-de JIANG ; Hong-de MA ; Xian-fei ZHONG ; Fang-wei XIE ; Wei-zheng ZENG
Chinese Journal of Hepatology 2003;11(11):650-653
OBJECTIVETo investigate the effect of PD98059 on the proliferation and cell cycle of rat hepatic stellate cells (HSCs) stimulated by acetaldehyde and explore its mechanism.
METHODSRat HSCs stimulated by acetaldehyde were incubated with different concentrations of PD98059. Cell proliferation was assessed by MTT colorimetric assay. Cell cycle was analysed by flow cytometry. The mRNA of cyclin D1 and CDK4 were examined by RT-PCR.
RESULTS20, 50, 100 micromol/L PD98059 could significantly inhibit the proliferation of HSCs stimulated by acetaldehyde in a does-dependent manner (0.109+/-0.020, 0.081+/-0.010 and 0.056+/-0.020 vs 0.146+/-0.030, F=31.385, P<0.05) and provoke G0/G1 phase arrest of HSCs stimulated by acetaldehyde in a does-dependent manner (61.9%+/-6.3%, 64.1%+/-3.3% and 70.9%+/-4.8% vs 55.2%+/-4.4%, F=16.402, P<0.05). 50, 100 micromol/L PD98059 could markedly inhibit cyclin D1 mRNA expression of HSC stimulated by acetaldehyde (0.56+/-0.04 and 0.46+/-0.03 vs 0.65+/-0.07, F=68.758, P<0.05) and CDK4 mRNA expression (0.39+/-0.07 and 0.33+/-0.05 vs 0.50+/-0.06, F=29.406, P<0.05).
CONCLUSIONThe Erk signal transduction pathway plays an important role in regulating the proliferation and cell cycle of rat hepatic stellate cells stimulated by acetaldehyde, which may be partly related to its regulative effect on the expression of cyclin D1 gene and CDK4 gene
Acetaldehyde ; pharmacology ; Animals ; Cells, Cultured ; Cyclin D1 ; metabolism ; Cyclin-Dependent Kinase 4 ; Cyclin-Dependent Kinases ; metabolism ; Enzyme Inhibitors ; pharmacology ; Flavonoids ; pharmacology ; Hepatocytes ; drug effects ; Proto-Oncogene Proteins ; Rats
5.Advances of the regulatory mechanism of cyclin, cyclin- dependent kinases and related kinase inhibitors in cell cycle progression.
Jianfeng PAN ; Fangzheng SHANG ; Rong MA ; Youjun RONG ; Yanjun ZHANG
Chinese Journal of Biotechnology 2023;39(4):1525-1547
Cell cycle plays a crucial role in cell development. Cell cycle progression is mainly regulated by cyclin dependent kinase (CDK), cyclin and endogenous CDK inhibitor (CKI). Among these, CDK is the main cell cycle regulator, binding to cyclin to form the cyclin-CDK complex, which phosphorylates hundreds of substrates and regulates interphase and mitotic progression. Abnormal activity of various cell cycle proteins can cause uncontrolled proliferation of cancer cells, which leads to cancer development. Therefore, understanding the changes in CDK activity, cyclin-CDK assembly and the role of CDK inhibitors will help to understand the underlying regulatory processes in cell cycle progression, as well as provide a basis for the treatment of cancer and disease and the development of CDK inhibitor-based therapeutic agents. This review focuses on the key events of CDK activation or inactivation, and summarizes the regulatory processes of cyclin-CDK at specific times and locations, as well as the progress of research on relevant CDK inhibitor therapeutics in cancer and disease. The review concludes with a brief description of the current challenges of the cell cycle process, with the aim to provide scientific references and new ideas for further research on cell cycle process.
Cyclin-Dependent Kinases/metabolism*
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Cyclins/metabolism*
;
Protein Serine-Threonine Kinases
;
Cell Cycle Proteins/metabolism*
;
Cell Cycle/physiology*
;
Cyclin-Dependent Kinase 2
6.Cyclin B1 and D1 expression in invasive cervical cancer.
Young Tae KIM ; Min ZHAO ; Hee Yeon KIM ; Moung Hwa KANG ; Jae Wook KIM ; Sung Hoon KIM ; Jae Hoon KIM ; Sang Wun KIM ; Bo Sung YOON
Korean Journal of Gynecologic Oncology 2005;16(3):256-263
OBJECTIVE: Cyclin is a family of regulatory proteins that play a key role in controlling the cell cycle. Abnormalities of cell cycle regulators, including cyclins and cyclin dependent kinases (CDKs), have been reported in malignant tumors. This study was undertaken to quantitatively detect cyclin B1 and D1 in cervical cancer. METHODS: A quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis were used to analyze the expression of cyclin B1, D1 mRNA and proteins, respectively, in fresh invasive cervical cancer (n=41) and normal cervix tissue (n=10). RESULTS: There was significantly greater cyclin B1 expression in invasive cervical cancer than in normal cervix tissue (p=0.019). However, cyclin D1 expression was not significantly different (p=0.967). A Western blot analysis yielded similar results. CONCLUSION: Our results were consistent with the concept that up-regulation of cyclin B1 expression occurred in cervical cancer and an aberrant expression of cyclin B1 might play an important role in cervical carcinogenesis.
Blotting, Western
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Carcinogenesis
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Cell Cycle
;
Cervix Uteri
;
Cyclin B1*
;
Cyclin D1
;
Cyclin I
;
Cyclin-Dependent Kinases
;
Cyclins*
;
Female
;
Humans
;
RNA, Messenger
;
Up-Regulation
;
Uterine Cervical Neoplasms*
7.The Clinical Significance of p21 Expressionin Gastric Adenocarcinoma.
Journal of the Korean Surgical Society 1998;55(1):65-69
BACKGROUNDS: The p21 protein inhibits cyclin-dependent kinases and mediates cell-cycle arrest and cell differentiation. METHODS: This study was performed in 61 patients with gastric adenocarcinoma to investigate the realtionship between p21 expression and clinicopathological findings, and the usefulness of p21 as a prognostic factor. Correlation was determined between p21 immunoreactivity by immunohistochemistry and clinicopathological features, including the clinical outcome. RESULTS: Immunoreactivity for p21 was detected in 31 (50.8%) patients. There were no significant correlations between the presence or absence of p21 immunoreactivity and age, sex, site, tumor invasion, tumor size, lymph node metastasis, distant metastasis, or stage except histologic subtype (P=0.002). Survival curves revealed that there was no significant difference of the prognosis between patients with p21 expression and those without p21 expression (P=0.836). CONCLUSIONS: Immunohistochemical analysis of p21 was not useful for evaluating the prognosis and biological status of patients with gastric adenocarcinoma.
Adenocarcinoma*
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Cell Differentiation
;
Cyclin-Dependent Kinases
;
Humans
;
Immunohistochemistry
;
Lymph Nodes
;
Neoplasm Metastasis
;
Prognosis
8.Dysregulation of Cell Cycle Regulating Proteins in Peripheral Lymphocytes from the Patients with Alzheimer's Disease.
Sung Ho CHUNG ; Young Ah KWON ; Hyeran KIM ; Ji Young SHIN ; Doh Kwan KIM
Korean Journal of Psychopharmacology 2004;15(4):474-479
OBJECTIVE: Extensive neuronal death occurring in the Alzheimer's disease (AD) may be related with the apoptosis. Recent studies have suggested that regulatory failure of cell cycle appeared to be very early event of AD pathogenesis in neuronal cells as well as in peripheral lymphocytes. We compared the change of cyclin dependent kinases (Cdks), which is related with G1/S phase transition in the cell cycle, between AD patients and normal controls using peripheral lymphocytes. METHODS: We obtained Cdks from peripheral lymphocytes of 37 AD patients and 18 age-matched normal subjects. Cells in first culture were considered to be G-zero (G0) cells. We measured Cdk2, Cdk4, and Cdk6 at baseline (T0). Thereafter, we observed Cdks 24 hours later after using PHA (phytohemaglutinin) (N24). Meanwhile, we observed Cdks 24 hours later again with rapamycin treatment (T24). RESULTS: At baseline (T0), Cdk2 and Cdk6 were increased in AD patients compared to the control group (p< 0.001, p=0.038, respectively). Cdk2 was increased in AD patients more than control group after using PHA (T24, p=0.007). After rapamycin treatment for 24 hours (N24), Cdk2, Cdk4, and Cdk6 were increased in the patients compared to the controls (p=0.002, p=0.022, p=0.011, respectively). CONCLUSION: This results showed that the cell cycle regulating proteins in AD patients, which are related with G1/S phase transition, were increased in peripheral lymphocytes compared to those in normal controls. We provide the clue which demonstrate the cell cycle dysregulation in the patients with Alzheimer's disease.
Alzheimer Disease*
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Apoptosis
;
Cell Cycle*
;
Cyclin-Dependent Kinases
;
Humans
;
Lymphocytes*
;
Neurons
;
Phase Transition
;
Sirolimus
9.Discovery of small molecule degraders for modulating cell cycle.
Liguo WANG ; Zhouli YANG ; Guangchen LI ; Yongbo LIU ; Chao AI ; Yu RAO
Frontiers of Medicine 2023;17(5):823-854
The cell cycle is a complex process that involves DNA replication, protein expression, and cell division. Dysregulation of the cell cycle is associated with various diseases. Cyclin-dependent kinases (CDKs) and their corresponding cyclins are major proteins that regulate the cell cycle. In contrast to inhibition, a new approach called proteolysis-targeting chimeras (PROTACs) and molecular glues can eliminate both enzymatic and scaffold functions of CDKs and cyclins, achieving targeted degradation. The field of PROTACs and molecular glues has developed rapidly in recent years. In this article, we aim to summarize the latest developments of CDKs and cyclin protein degraders. The selectivity, application, validation and the current state of each CDK degrader will be overviewed. Additionally, possible methods are discussed for the development of degraders for CDK members that still lack them. Overall, this article provides a comprehensive summary of the latest advancements in CDK and cyclin protein degraders, which will be helpful for researchers working on this topic.
Humans
;
Cell Cycle/physiology*
;
Cell Division
;
Cyclin-Dependent Kinases/metabolism*
;
Cyclins/metabolism*
10.Abnormal Mitochondria in a Non-human Primate Model of MPTP-induced Parkinson's Disease: Drp1 and CDK5/p25 Signaling
Junghyung PARK ; Jincheol SEO ; Jinyoung WON ; Hyeon Gu YEO ; Yu Jin AHN ; Keonwoo KIM ; Yeung Bae JIN ; Bon Sang KOO ; Kyung Seob LIM ; Kang Jin JEONG ; Philyong KANG ; Hwal Yong LEE ; Seung Ho BAEK ; Chang Yeop JEON ; Jung Joo HONG ; Jae Won HUH ; Young Hyun KIM ; Sang Je PARK ; Sun Uk KIM ; Dong Seok LEE ; Sang Rae LEE ; Youngjeon LEE
Experimental Neurobiology 2019;28(3):414-424
Mitochondria continuously fuse and divide to maintain homeostasis. An impairment in the balance between the fusion and fission processes can trigger mitochondrial dysfunction. Accumulating evidence suggests that mitochondrial dysfunction is related to neurodegenerative diseases such as Parkinson's disease (PD), with excessive mitochondrial fission in dopaminergic neurons being one of the pathological mechanisms of PD. Here, we investigated the balance between mitochondrial fusion and fission in the substantia nigra of a non-human primate model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD. We found that MPTP induced shorter and abnormally distributed mitochondria. This phenomenon was accompanied by the activation of dynamin-related protein 1 (Drp1), a mitochondrial fission protein, through increased phosphorylation at S616. Thereafter, we assessed for activation of the components of the cyclin-dependent kinase 5 (CDK5) and extracellular signal-regulated kinase (ERK) signaling cascades, which are known regulators of Drp1(S616) phosphorylation. MPTP induced an increase in p25 and p35, which are required for CDK5 activation. Together, these findings suggest that the phosphorylation of Drp1(S616) by CDK5 is involved in mitochondrial fission in the substantia nigra of a non-human primate model of MPTP-induced PD.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
;
Cyclin-Dependent Kinase 5
;
Cyclin-Dependent Kinases
;
Dopaminergic Neurons
;
Homeostasis
;
Mitochondria
;
Mitochondrial Dynamics
;
Neurodegenerative Diseases
;
Parkinson Disease
;
Phosphorylation
;
Phosphotransferases
;
Primates
;
Substantia Nigra