Future Therapy for HBV: Role of Cell Cycle Inhibitors

2016 ◽  
Vol 15 (4) ◽  
pp. 245-251 ◽  
Author(s):  
Mayur Brahmania ◽  
Harry L. A. Janssen
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Inhibitors ◽  
Future Therapy

scholarly journals MYC Oncogene Contributions to Release of Cell Cycle Brakes

Genes ◽  
2019 ◽  
Vol 10 (3) ◽  
pp. 244 ◽  
Author(s):  
Lucía García-Gutiérrez ◽  
María Dolores Delgado ◽  
Javier León
Keyword(s):  
Cell Cycle ◽  
Transcriptional Level ◽  
Synthetic Lethal ◽  
Myc Oncogene ◽  
Synthetic Lethal Interactions ◽  
A Cell ◽  
Functional Inactivation ◽  
P27 Gene ◽  
Cell Cycle Inhibitors

Promotion of the cell cycle is a major oncogenic mechanism of the oncogene c-MYC (MYC). MYC promotes the cell cycle by not only activating or inducing cyclins and CDKs but also through the downregulation or the impairment of the activity of a set of proteins that act as cell-cycle brakes. This review is focused on the role of MYC as a cell-cycle brake releaser i.e., how MYC stimulates the cell cycle mainly through the functional inactivation of cell cycle inhibitors. MYC antagonizes the activities and/or the expression levels of p15, ARF, p21, and p27. The mechanism involved differs for each protein. p15 (encoded by CDKN2B) and p21 (CDKN1A) are repressed by MYC at the transcriptional level. In contrast, MYC activates ARF, which contributes to the apoptosis induced by high MYC levels. At least in some cells types, MYC inhibits the transcription of the p27 gene (CDKN1B) but also enhances p27’s degradation through the upregulation of components of ubiquitin ligases complexes. The effect of MYC on cell-cycle brakes also opens the possibility of antitumoral therapies based on synthetic lethal interactions involving MYC and CDKs, for which a series of inhibitors are being developed and tested in clinical trials

scholarly journals The role of AUF1 in thyroid carcinoma progression

2009 ◽  
Vol 16 (3) ◽  
pp. 857-871 ◽  
Author(s):  
Bogusz Trojanowicz ◽  
Lars Brodauf ◽  
Carsten Sekulla ◽  
Kerstin Lorenz ◽  
Rainer Finke ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Thyroid Carcinoma ◽  
Growth Regulation ◽  
Kinase Inhibitors ◽  
Carcinoma Cell Lines ◽  
Dividing Cells ◽  
The Stability ◽  
Nuclear Ribonucleoprotein ◽  
Cell Cycle Inhibitors

AUF1/heterogeneous nuclear ribonucleoprotein D is an adenylate–uridylate-rich elements (AREs) -binding protein, which regulates the mRNA stability of many genes related to growth regulation, such as proto-oncogenes, growth factors, cytokines, and cell cycle-regulatory genes. Several studies demonstrated AUF1 involvement in the processes of apoptosis, tumorigenesis, and development by its interactions with ARE-bearing mRNAs. We report here that AUF1 may be involved in thyroid carcinoma progression. Investigations on thyroid tissues revealed that cytoplasmic expression of AUF1 in malignant tissues was increased when compared with benign thyroid tissues. In thyroid carcinoma cell lines, AUF1 was mostly detectable in the nucleus; however, in dividing cells, its increased production was also observed in the cytoplasm. We found AUF1 in complexes with ARE-bearing mRNAs, previously described to be crucial for proliferation and cell cycle of thyroid carcinoma. Total or exon-selective knockdown of AUF1 led to growth inhibition accompanied by induction of cell cycle inhibitors and decreased levels of cell cycle promoters. Our data demonstrate the existence of a complex network between AUF1 and mRNAs encoding proteins related to cell proliferation. AUF1 may control the balance between stabilizing and destabilizing effects, both of which are exerted on cell cycle machinery in thyroid carcinoma. Although we cannot exclude participation of other factors, thyroid carcinoma may recruit cytoplasmic AUF1 to disturb the stability of mRNAs encoding cyclin-dependent kinase inhibitors, leading to uncontrolled growth and progression of tumor cells. Thus, AUF1 may be considered as a new, additional marker for thyroid carcinoma.

scholarly journals Expression of cell cycle inhibitors in canine prostate with proliferative inflammatory atrophy and carcinoma

2018 ◽  
Vol 70 (1) ◽  
pp. 82-92
Author(s):  
M.B.R. Faleiro ◽  
L.C. Cintra ◽  
R.S.A. Jesuino ◽  
A.D. Damasceno ◽  
V.M.B.D. Moura
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Prostatic Carcinoma ◽  
Protective Factor ◽  
Ffpe Tissue ◽  
Rt Pcr ◽  
Normal Tissues ◽  
Proliferative Inflammatory Atrophy ◽  
Cell Cycle Inhibitors

ABSTRACT Gene expression of CDKN1A, CDKN1B, and TP53, and immunostaining of p21, p27 and p53 were evaluated to verify the role of these cell cycle inhibitors in canine prostates with proliferative inflammatory atrophy-PIA and prostatic carcinoma-PC. Seventy samples, 15 normal, 30PIA and 25PC. Regarding number of p27 and p53 labeled cells, difference between normal and PIA and PC was observed, as well as between PIA and PC for p53. Immunostaining intensities of p21, p27 and p53 were different when comparing normal tissues to PIA and PC. Sixteen cDNA of canine prostatic FFPE tissue were subjected to RT-PCR and RT-qPCR, four normal, three PIA, and nine PC. CDKN1A mRNA was detected in four PC by RT-PCR, and it was overexpressed when compared to normal by RT-qPCR, in one PIA and six PC. CDKN1B mRNA was detected in three PC by RT-PCR and it was overexpressed in three PC and decreased in one PC. TP53 mRNA was overexpressed in one PIA and three PC. In conclusion, when overexpressed in canine prostate with premalignant and malignant, p21 and p27 play a role controlling cell proliferation, working as a protective factor in the evolution of PIA to PC, and in the PC development, even in the presence of altered p53.

Biological Role of CDK 11 and 12 in Cell Cycle and its Function in Tumorigenesis

2020 ◽  
Author(s):  
Shamim Mushtaq
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Web Of Science ◽  
The Body ◽  
Main Role ◽  
Hallmarks Of Cancer ◽  
Cyclin Dependent Kinases ◽  
Tumor Studies ◽  
Cycle Regulation

Uninhibited proliferation and abnormal cell cycle regulation are the hallmarks of cancer. The main role of cyclin dependent kinases is to regulate the cell cycle and cell proliferation. These protein kinases are frequently down regulated or up regulated in various cancers. Two CDK family members, CDK 11 and 12, have contradicting views about their roles in different cancers. For example, one study suggests that the CDK 11 isoforms, p58, inhibits growth of breast cancer whereas, the CDK 11 isoform, p110, is highly expressed in breast tumor. Studies regarding CDK 12 show variation of opinion towards different parts of the body, however there is a consensus that upregulation of cdk12 increases the risk of breast cancer. Hence, CDK 11 and CDK 12 need to be analyzed to confirm their mechanism and their role regarding therapeutics, prognostic value, and ethnicity in cancer. This article gives an outline on both CDKs of information known up to date from Medline, PubMed, Google Scholar and Web of Science search engines, which were explored and thirty relevant researches were finalized.

PTTG has a Dual Role of Promotion-Inhibition in the Development of Pituitary Adenomas

2019 ◽  
Vol 26 (11) ◽  
pp. 800-818
Author(s):  
Zujian Xiong ◽  
Xuejun Li ◽  
Qi Yang
Keyword(s):  
Cell Cycle ◽  
Pituitary Adenoma ◽  
Pituitary Adenomas ◽  
Cell Cycle Progression ◽  
Key Factors ◽  
Cycle Progression ◽  
Sister Chromatids ◽  
Regulation Of Cell Cycle ◽  
Late Stages

Pituitary Tumor Transforming Gene (PTTG) of human is known as a checkpoint gene in the middle and late stages of mitosis, and is also a proto-oncogene that promotes cell cycle progression. In the nucleus, PTTG works as securin in controlling the mid-term segregation of sister chromatids. Overexpression of PTTG, entering the nucleus with the help of PBF in pituitary adenomas, participates in the regulation of cell cycle, interferes with DNA repair, induces genetic instability, transactivates FGF-2 and VEGF and promotes angiogenesis and tumor invasion. Simultaneously, overexpression of PTTG induces tumor cell senescence through the DNA damage pathway, making pituitary adenoma possessing the potential self-limiting ability. To elucidate the mechanism of PTTG in the regulation of pituitary adenomas, we focus on both the positive and negative function of PTTG and find out key factors interacted with PTTG in pituitary adenomas. Furthermore, we discuss other possible mechanisms correlate with PTTG in pituitary adenoma initiation and development and the potential value of PTTG in clinical treatment.

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