scholarly journals Ki-67 gene expression

2021 ◽  
Author(s):  
Sigrid Uxa ◽  
Paola Castillo-Binder ◽  
Robin Kohler ◽  
Konstanze Stangner ◽  
Gerd A. Müller ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Tumor Suppressor ◽  
Transcriptional Repression ◽  
Transcriptional Control ◽  
Ki 67 ◽  
Gene Coding ◽  
P53 Activation ◽  
Retinoblastoma Tumor ◽  
Cycle Dependent

AbstractKi-67 serves as a prominent cancer marker. We describe how expression of the MKI67 gene coding for Ki-67 is controlled during the cell cycle. MKI67 mRNA and Ki-67 protein are maximally expressed in G2 phase and mitosis. Expression is dependent on two CHR elements and one CDE site in the MKI67 promoter. DREAM transcriptional repressor complexes bind to both CHR sites and downregulate the expression in G0/G1 cells. Upregulation of MKI67 transcription coincides with binding of B-MYB-MuvB and FOXM1-MuvB complexes from S phase into G2/M. Importantly, binding of B-MYB to the two CHR elements correlates with loss of CHR-dependent MKI67 promoter activation in B-MYB-knockdown experiments. In knockout cell models, we find that DREAM/MuvB-dependent transcriptional control cooperates with the RB Retinoblastoma tumor suppressor. Furthermore, the p53 tumor suppressor indirectly downregulates transcription of the MKI67 gene. This repression by p53 requires p21/CDKN1A. These results are consistent with a model in which DREAM, B-MYB-MuvB, and FOXM1-MuvB together with RB cooperate in cell cycle-dependent transcription and in transcriptional repression following p53 activation. In conclusion, we present mechanisms how MKI67 gene expression followed by Ki-67 protein synthesis is controlled during the cell cycle and upon induction of DNA damage, as well as upon p53 activation.

scholarly journals Retinoblastoma Tumor Suppressor: Analyses of Dynamic Behavior in Living Cells Reveal Multiple Modes of Regulation

2003 ◽  
Vol 23 (22) ◽  
pp. 8172-8188 ◽  
Author(s):  
Steven P. Angus ◽  
David A. Solomon ◽  
Lioba Kuschel ◽  
Robert F. Hennigan ◽  
Erik S. Knudsen
Keyword(s):  
Cell Cycle ◽  
Tumor Suppressor ◽  
Dynamic Behavior ◽  
Transcriptional Repression ◽  
Fluorescent Protein ◽  
Dynamic Equilibrium ◽  
Living Cells ◽  
Retinoblastoma Tumor Suppressor ◽  
Retinoblastoma Tumor

ABSTRACT The retinoblastoma tumor suppressor, RB, assembles multiprotein complexes to mediate cell cycle inhibition. Although many RB binding partners have been suggested to underlie these functions, the validity of these interactions on the behavior of RB complexes in living cells has not been investigated. Here, we studied the dynamic behavior of RB by using green fluorescent protein-RB fusion proteins. Although these proteins were universally nuclear, phosphorylation or oncoprotein binding mediated their active exclusion from the nucleolus. In vivo imaging approaches revealed that RB exists in dynamic equilibrium between a highly mobile and a slower diffusing species, and genetic lesions associated with tumorigenesis increased the fraction of RB in a highly mobile state. The RB complexes dictating cell cycle arrest were surprisingly dynamic and harbored a relatively short residence time on chromatin. In contrast, this rapid exchange was attenuated in cells that are hypersensitive to RB, suggesting that responsiveness may inversely correlate with mobility. The stability of RB dynamics within the cell was additionally modified by the presence and function of critical corepressors. Last, the RB-assembled complexes present in living cells were primarily associated with E2F binding sites in chromatin. In contrast to RB, E2F1 consistently maintained a stable association with E2F sites regardless of cell type. Together, these results elucidate the kinetic framework of RB tumor suppressor action in transcriptional repression and cell cycle regulation.

scholarly journals Heterochromatic foci and transcriptional repression by an unstructured MET-2/SETDB1 co-factor LIN-65

2019 ◽  
Vol 218 (3) ◽  
pp. 820-838 ◽  
Author(s):  
Colin E. Delaney ◽  
Stephen P. Methot ◽  
Micol Guidi ◽  
Iskra Katic ◽  
Susan M. Gasser ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mass Spectrometry ◽  
Cell Cycle ◽  
Stress Resistance ◽  
Transcriptional Repression ◽  
Dependent Manner ◽  
A Cell ◽  
H3k9 Dimethylation ◽  
Cycle Dependent ◽  
Unstructured Protein

The segregation of the genome into accessible euchromatin and histone H3K9-methylated heterochromatin helps silence repetitive elements and tissue-specific genes. In Caenorhabditis elegans, MET-2, the homologue of mammalian SETDB1, catalyzes H3K9me1 and me2, yet like SETDB1, its regulation is enigmatic. Contrary to the cytosolic enrichment of overexpressed MET-2, we show that endogenous MET-2 is nuclear throughout development, forming perinuclear foci in a cell cycle–dependent manner. Mass spectrometry identified two cofactors that bind MET-2: LIN-65, a highly unstructured protein, and ARLE-14, a conserved GTPase effector. All three factors colocalize in heterochromatic foci. Ablation of lin-65, but not arle-14, mislocalizes and destabilizes MET-2, resulting in decreased H3K9 dimethylation, dispersion of heterochromatic foci, and derepression of MET-2 targets. Mutation of met-2 or lin-65 also disrupts the perinuclear anchoring of genomic heterochromatin. Loss of LIN-65, like that of MET-2, compromises temperature stress resistance and germline integrity, which are both linked to promiscuous repeat transcription and gene expression.

Cell cycle-dependent reactivity with the monoclonal antibody Ki-67 during myeloid cell differentiation

1988 ◽  
Vol 179 (1) ◽  
pp. 79-88 ◽  
Author(s):  
Robert P. Wersto ◽  
Fritz Herz ◽  
Robert E. Gallagher ◽  
Leopold G. Koss
Keyword(s):  
Cell Cycle ◽  
Monoclonal Antibody ◽  
Cell Differentiation ◽  
Myeloid Cell ◽  
Ki 67 ◽  
Cycle Dependent

scholarly journals The DREAM complex: master coordinator of cell cycle-dependent gene expression

2013 ◽  
Vol 13 (8) ◽  
pp. 585-595 ◽  
Author(s):  
Subhashini Sadasivam ◽  
James A. DeCaprio
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cycle Dependent

scholarly journals A Novel Transcriptional Repression Domain Mediates p21WAF1/CIP1 Induction of p300 Transactivation

2000 ◽  
Vol 20 (8) ◽  
pp. 2676-2686 ◽  
Author(s):  
Andrew W. Snowden ◽  
Lisa A. Anderson ◽  
Gill A. Webster ◽  
Neil D. Perkins
Keyword(s):  
Cell Cycle ◽  
Transcriptional Activation ◽  
Transcriptional Repression ◽  
Kinase Inhibitor ◽  
Core Promoter ◽  
Dependent Manner ◽  
Creb Binding Protein ◽  
Cycle Dependent ◽  
Repression Domain

ABSTRACT The transcriptional coactivators p300 and CREB binding protein (CBP) are important regulators of the cell cycle, differentiation, and tumorigenesis. Both p300 and CBP are targeted by viral oncoproteins, are mutated in certain forms of cancer, are phosphorylated in a cell cycle-dependent manner, interact with transcription factors such as p53 and E2F, and can be found complexed with cyclinE-Cdk2 in vivo. Moreover, p300-deficient cells show defects in proliferation. Here we demonstrate that transcriptional activation by both p300 and CBP is stimulated by coexpression of the cyclin-dependent kinase inhibitor p21WAF/CIP1. Significantly this stimulation is independent of both the inherent histone acetyltransferase (HAT) activity of p300 and CBP and of the previously reported carboxyl-terminal binding site for cyclinE-Cdk2. Rather, we describe a previously uncharacterized transcriptional repression domain (CRD1) within p300. p300 transactivation is stimulated through derepression of CRD1 by p21. Significantly p21 regulation of CRD1 is dependent on the nature of the core promoter. We suggest that CRD1 provides a novel mechanism through which p300 and CBP can switch activities between the promoters of genes that stimulate growth and those that enhance cell cycle arrest.

Sign in / Sign up

Export Citation Format

Share Document