scholarly journals APRIN is a cell cycle specific BRCA2-interacting protein required for genome integrity and a predictor of outcome after chemotherapy in breast cancer

2012 ◽  
Vol 31 (5) ◽  
pp. 1160-1176 ◽  
Author(s):  
Rachel Brough ◽  
Ilirjana Bajrami ◽  
Radost Vatcheva ◽  
Rachael Natrajan ◽  
Jorge S Reis-Filho ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Genome Integrity ◽  
Interacting Protein ◽  
A Cell

scholarly journals Binding of STIL to Plk4 activates kinase activity to promote centriole assembly

2015 ◽  
Vol 209 (6) ◽  
pp. 863-878 ◽  
Author(s):  
Tyler C. Moyer ◽  
Kevin M. Clutario ◽  
Bramwell G. Lambrus ◽  
Vikas Daggubati ◽  
Andrew J. Holland
Keyword(s):  
Cell Cycle ◽  
Gene Editing ◽  
Genetic System ◽  
Genome Integrity ◽  
Chemical Genetic ◽  
Centriole Duplication ◽  
C Terminus ◽  
A Cell ◽  
Direct Binding ◽  
Centriole Assembly

Centriole duplication occurs once per cell cycle in order to maintain control of centrosome number and ensure genome integrity. Polo-like kinase 4 (Plk4) is a master regulator of centriole biogenesis, but how its activity is regulated to control centriole assembly is unclear. Here we used gene editing in human cells to create a chemical genetic system in which endogenous Plk4 can be specifically inhibited using a cell-permeable ATP analogue. Using this system, we demonstrate that STIL localization to the centriole requires continued Plk4 activity. Most importantly, we show that direct binding of STIL activates Plk4 by promoting self-phosphorylation of the activation loop of the kinase. Plk4 subsequently phosphorylates STIL to promote centriole assembly in two steps. First, Plk4 activity promotes the recruitment of STIL to the centriole. Second, Plk4 primes the direct binding of STIL to the C terminus of SAS6. Our findings uncover a molecular basis for the timing of Plk4 activation through the cell cycle–regulated accumulation of STIL.

scholarly journals Gene Expression Alterations Associated with Oleuropein-Induced Antiproliferative Effects and S-Phase Cell Cycle Arrest in Triple-Negative Breast Cancer Cells

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3755
Author(s):  
Samia S. Messeha ◽  
Najla O. Zarmouh ◽  
Abrar Asiri ◽  
Karam F. A. Soliman
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cell Cycle ◽  
Cell Lines ◽  
Triple Negative ◽  
S Phase ◽  
Phase Cell ◽  
Tnf Receptor ◽  
Interacting Protein ◽  
Cycle Arrest

It is known that the Mediterranean diet is effective in reducing the risk of several chronic diseases, including cancer. A critical component of the Mediterranean diet is olive oil, and the relationship between olive oil consumption and the reduced risk of cancer has been established. Oleuropein (OL) is the most prominent polyphenol component of olive fruits and leaves. This compound has been shown to have potent properties in various types of cancers, including breast cancer. In the present study, the molecular mechanism of OL was examined in two racially different triple-negative breast cancer (TNBC) cell lines—African American (AA, MDA-MB-468) and Caucasian American (CA, MDA-MB-231). The data obtained showed that OL effectively inhibits cell growth in both cell lines, concomitant with S-phase cell cycle arrest-mediated apoptosis. The results also showed that OL-treated MDA-MB-468 cells were two-fold more sensitive to OL antiproliferative effect than MDA-MB-231 cells were. At lower concentrations, OL modified the expression of many apoptosis-involved genes. OL was more effective in MDA-MB-468, compared to MDA-MB-231 cells, in terms of the number and the fold-change of the altered genes. In MDA-MB-468 cells, OL induced a noticeable transcription activation in fourteen genes, including two members of the caspase family: caspase 1 (CASP1) and caspase 14 (CASP14); two members of the TNF receptor superfamily: Fas-associated via death domain (FADD) and TNF receptor superfamily 21 (TNFRSF21); six other proapoptotic genes: growth arrest and DNA damage-inducible 45 alpha (GADD45A), cytochrome c somatic (CYCS), BCL-2 interacting protein 2 (BNIP2), BCL-2 interacting protein 3 (BNIP3), BH3 interacting domain death agonist (BID), and B-cell lymphoma/leukemia 10 (BCL10); and the CASP8 and FADD-like apoptosis regulator (CFLAR) gene. Moreover, in MDA-MB-468 cells, OL induced a significant upregulation in two antiapoptotic genes: bifunctional apoptosis regulator (BFAR) and B-Raf proto-oncogene (BRAF) and a baculoviral inhibitor of apoptosis (IAP) repeat-containing 3 (BIRC3). On the contrary, in MDA-MB-231 cells, OL showed mixed impacts on gene expression. OL significantly upregulated the mRNA expression of four genes: BIRC3, receptor-interacting serine/threonine kinase 2 (RIPK2), TNF receptor superfamily 10A (TNFRSF10A), and caspase 4 (CASP4). Additionally, another four genes were repressed, including caspase 6 (CASP6), pyrin domain (PYD), and caspase recruitment domain (CARD)-containing (PAYCARD), baculoviral IAP repeat-containing 5 (BIRC5), and the most downregulated TNF receptor superfamily member 11B (TNFRSF11B, 16.34-fold). In conclusion, the data obtained indicate that the two cell lines were markedly different in the anticancer effect and mechanisms of oleuropein’s ability to alter apoptosis-related gene expressions. The results obtained from this study should also guide the potential utilization of oleuropein as an adjunct therapy for TNBC to increase chemotherapy effectiveness and prevent cancer progression.

scholarly journals CEP120 interacts with CPAP and positively regulates centriole elongation

2013 ◽  
Vol 202 (2) ◽  
pp. 211-219 ◽  
Author(s):  
Yi-Nan Lin ◽  
Chien-Ting Wu ◽  
Yu-Chih Lin ◽  
Wen-Bin Hsu ◽  
Chieh-Ju C. Tang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dimerization Domain ◽  
Interacting Protein ◽  
Centrosomal Protein ◽  
Microtubule Binding ◽  
Protein 4.1 ◽  
Centriole Duplication ◽  
Localization Domain ◽  
Microtubule Binding Domain ◽  
A Cell

Centriole duplication begins with the formation of a single procentriole next to a preexisting centriole. CPAP (centrosomal protein 4.1–associated protein) was previously reported to participate in centriole elongation. Here, we show that CEP120 is a cell cycle–regulated protein that directly interacts with CPAP and is required for centriole duplication. CEP120 levels increased gradually from early S to G2/M and decreased significantly after mitosis. Forced overexpression of either CEP120 or CPAP not only induced the assembly of overly long centrioles but also produced atypical supernumerary centrioles that grew from these long centrioles. Depletion of CEP120 inhibited CPAP-induced centriole elongation and vice versa, implying that these proteins work together to regulate centriole elongation. Furthermore, CEP120 was found to contain an N-terminal microtubule-binding domain, a C-terminal dimerization domain, and a centriolar localization domain. Overexpression of a microtubule binding–defective CEP120-K76A mutant significantly suppressed the formation of elongated centrioles. Together, our results indicate that CEP120 is a CPAP-interacting protein that positively regulates centriole elongation.

scholarly journals Cyclin B2 (CCNB2) Stimulates the Proliferation of Triple-Negative Breast Cancer (TNBC) Cells In Vitro and In Vivo

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Shuai Wu ◽  
Rui Su ◽  
Hongyan Jia
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Triple Negative Breast Cancer ◽  
Potential Role ◽  
Triple Negative ◽  
Targeting Therapy ◽  
A Cell

Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer. Currently, targeting therapy makes great advances for the treatment of TNBC, whereas more effective therapeutic targets are urgently needed. Cyclin B2 (CCNB2), which belongs to B-type cyclins, is known as a cell cycle regulator. CCNB2 is synthesized at G1 phase in cancer cells and downregulated at anaphase. The defects of CCNB2 led to the abnormal cell cycle and tumorigenesis. Though there are wide effects of CCNB2 on multiple types of tumors, the potential role of CCNB2 in TNBC progression is still unclear. Herein, we found that CCNB2 was highly expressed in human TNBC tissues and correlated with the prognosis and clinical pathological features including tumor size ( p = 0.022 ∗ ) and pTNM stage ( p = 0.021 ∗ ) of patients with TNBC. CCNB2 could promote the proliferation of TNBC cells in vitro and in mice. Our findings therefore confirmed the involvement of CCNB2 in TNBC progression and provided the evidence that CCNB2 could serve as a promising molecular target of TNBC.

scholarly journals Septin-Dependent Assembly of a Cell Cycle-Regulatory Module in Saccharomyces cerevisiae

2000 ◽  
Vol 20 (11) ◽  
pp. 4049-4061 ◽  
Author(s):  
Mark S. Longtine ◽  
Chandra L. Theesfeld ◽  
John N. McMillan ◽  
Elizabeth Weaver ◽  
John R. Pringle ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Detectable Effect ◽  
Direct Role ◽  
Interacting Protein ◽  
Actin Organization ◽  
Cell Cycle Delay ◽  
A Cell ◽  
Morphogenesis Checkpoint ◽  
P21 Activated Kinase

ABSTRACT Saccharomyces cerevisiae septin mutants have pleiotropic defects, which include the formation of abnormally elongated buds. This bud morphology results at least in part from a cell cycle delay imposed by the Cdc28p-inhibitory kinase Swe1p. Mutations in three other genes (GIN4, encoding a kinase related to the Schizosaccharomyces pombe mitotic inducer Nim1p; CLA4, encoding a p21-activated kinase; andNAP1, encoding a Clb2p-interacting protein) also produce perturbations of septin organization associated with an Swe1p-dependent cell cycle delay. The effects of gin4, cla4, and nap1 mutations are additive, indicating that these proteins promote normal septin organization through pathways that are at least partially independent. In contrast, mutations affecting the other two Nim1p-related kinases in S. cerevisiae, Hsl1p and Kcc4p, produce no detectable effect on septin organization. However, deletion of HSL1, but not of KCC4, did produce a cell cycle delay under some conditions; this delay appears to reflect a direct role of Hsl1p in the regulation of Swe1p. As shown previously, Swe1p plays a central role in the morphogenesis checkpoint that delays the cell cycle in response to defects in bud formation. Swe1p is localized to the nucleus and to the daughter side of the mother bud neck prior to its degradation in G2/M phase. Both the neck localization of Swe1p and its degradation require Hsl1p and its binding partner Hsl7p, both of which colocalize with Swe1p at the daughter side of the neck. This localization is lost in mutants with perturbed septin organization, suggesting that the release of Hsl1p and Hsl7p from the neck may reduce their ability to inactivate Swe1p and thus contribute to the G2 delay observed in such mutants. In contrast, treatments that perturb actin organization have little effect on Hsl1p and Hsl7p localization, suggesting that such treatments must stabilize Swe1p by another mechanism. The apparent dependence of Swe1p degradation on localization of the Hsl1p-Hsl7p-Swe1p module to a site that exists only in budded cells may constitute a mechanism for deactivating the morphogenesis checkpoint when it is no longer needed (i.e., after a bud has formed).

The oncoprotein HBXIP – its functions and roles in oncogenesis

2018 ◽  
Vol 8 (2) ◽  
pp. 215-222
Author(s):  
M. Grudzinska ◽  
K. Lomperta ◽  
K. Jakubowska ◽  
P. Samocik ◽  
K. Jarząbek ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Treatment Effectiveness ◽  
Malignant Tumors ◽  
Interacting Protein ◽  
Complement Dependent Cytotoxicity ◽  
Tumor Tissues ◽  
A Cell ◽  
Cancerous Cells

Nowadays, Hepatitis B X interacting protein (HBXIP) is an object of scientists’ interest worldwide. It is a protein with significant involvement in the development of malignant tumors like breast or ovarian cancer. One of the most important functions of HBXIP is the regulation of cell proliferation, which is related to the progression of a cell cycle. Many studies provide the growing number of evidence that HBXIP plays various important roles, including the regulation of a cell cycle through complexes with survivin, belonging to the inhibitors of apoptosis and interactions with transcriptional factors like STAT4, SP1, TFIID or E2F1. It also has the influence on the promotion of tumor angiogenesis thanks to the association with VEGF and FGF8. Another important role of HBXIP is a reprogramming of glucose metabolism to conditions favorable to growing cancerous cells due to regulating the activation of SCO2 and PDHA1. Furthermore, it impacts on the complement-dependent cytotoxicity, also, HBXIP affects on lipid metabolism through disturbing of metabolic pathways of FAS. According to recent studies, HBXIP can be used as a prognostic biomarker in many tumors, including cervical cancer, ovarian cancer, and esophageal squamous cell carcinoma thanks to the high expression of this protein noted exclusively in these tumor tissues. What is even more interesting, it significantly correlates with clinical attributes like metastasis to lymph nodes or grading and in some cases can potentially be used as the indicator of prognosis of treatment effectiveness. The paper is review through main functions of HBXIP and its possible applications.

357: Interstitial Cystitis Anti-Proliferative Factor (APF) as a Cell-Cycle Modulator

2004 ◽  
Vol 171 (4S) ◽  
pp. 93-94
Author(s):  
Hani Rashid ◽  
Susan Keay ◽  
Chen-Ou Zhang ◽  
Edward M. Messing ◽  
Jay Reeder
Keyword(s):  
Cell Cycle ◽  
Interstitial Cystitis ◽  
A Cell
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