scholarly journals Cell Cycle–Dependent Nuclear Export of Phosphatase and Tensin Homologue Tumor Suppressor Is Regulated by the Phosphoinositide-3-Kinase Signaling Cascade

2007 ◽  
Vol 67 (22) ◽  
pp. 11054-11063 ◽  
Author(s):  
Juinn-Lin Liu ◽  
Zhenyu Mao ◽  
Tiffany A. LaFortune ◽  
Marta M. Alonso ◽  
Gary E. Gallick ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Tumor Suppressor ◽  
Nuclear Export ◽  
Signaling Cascade ◽  
Kinase Signaling ◽  
Phosphoinositide 3 Kinase ◽  
Cycle Dependent ◽  
Phosphatase And Tensin Homologue

Optimal B-cell proliferation requires phosphoinositide 3-kinase–dependent inactivation of FOXO transcription factors

Blood ◽  
2004 ◽  
Vol 104 (3) ◽  
pp. 784-787 ◽  
Author(s):  
Isharat Yusuf ◽  
Xiaocui Zhu ◽  
Michael G. Kharas ◽  
Jing Chen ◽  
David A. Fruman
Keyword(s):  
Cell Cycle ◽  
Transcription Factors ◽  
B Cells ◽  
B Cell ◽  
Nuclear Export ◽  
Cell Cycle Progression ◽  
B Lymphocyte ◽  
Cell Receptor ◽  
Dependent Inactivation ◽  
Phosphoinositide 3 Kinase

AbstractTranscription factors of the Forkhead Box, class O (FOXO) family promote cell-cycle arrest and/or apoptosis in a variety of cell types. Mitogenic stimuli inactivate FOXO function by way of an evolutionarily conserved pathway involving the activation of phosphoinositide 3-kinase (PI3K) and its downstream effector, Akt. Although PI3K activation is required for B-lymphocyte proliferation, it is not known whether PI3K-dependent inactivation of FOXO proteins is important for cell-cycle progression and survival of these cells. Here, we show that B-cell receptor (BCR) engagement triggers PI3K-dependent phosphorylation and nuclear export of FOXO1. Furthermore, forced expression of PI3K-independent variants of FOXO1 or FOXO3a in activated B cells induces partial arrest in G1 phase of the cell cycle and increases apoptosis. These findings establish that FOXO inactivation is a functionally important consequence of PI3K signaling in primary B cells.

scholarly journals Nucleocytoplasmic Shuttling of the Cdc42p Exchange Factor Cdc24p

2000 ◽  
Vol 148 (6) ◽  
pp. 1115-1122 ◽  
Author(s):  
Aljoscha Nern ◽  
Robert A. Arkowitz
Keyword(s):  
Cell Cycle ◽  
Actin Cytoskeleton ◽  
Nuclear Import ◽  
Vegetative Growth ◽  
Nuclear Export ◽  
Nuclear Accumulation ◽  
Nucleocytoplasmic Shuttling ◽  
Exchange Factor ◽  
Cycle Dependent ◽  
Necessary And Sufficient

Cdc24p, the GDP/GTP exchange factor for the regulator of actin cytoskeleton Cdc42p, localizes to sites of polarized growth. Here we show that Cdc24p shuttles in and out of the yeast nucleus during vegetative growth. Far1p is necessary and sufficient for nuclear accumulation of Cdc24p, suggesting that its nuclear import occurs via an association with Far1p. Nuclear export is triggered either by entry into the cell cycle or by mating pheromone. As Far1p is degraded upon entry into the cell cycle, cell cycle–dependent export of Cdc24p occurs in the absence of Far1p, whereas during mating similar export kinetics indicate that a Cdc24p–Far1p complex is exported. Our results suggest that the nucleus serves as a store of preformed Cdc24p–Far1p complex which is required for chemotropism.

scholarly journals Identification of Novel Saccharomyces cerevisiaeProteins with Nuclear Export Activity: Cell Cycle-Regulated Transcription Factor Ace2p Shows Cell Cycle-Independent Nucleocytoplasmic Shuttling

2000 ◽  
Vol 20 (21) ◽  
pp. 8047-8058 ◽  
Author(s):  
Torben Heick Jensen ◽  
Megan Neville ◽  
Jean Christophe Rain ◽  
Terri McCarthy ◽  
Pierre Legrain ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Transcription Factor ◽  
Nuclear Export ◽  
Consensus Sequence ◽  
Dependent Manner ◽  
Reading Frame ◽  
Export Activity ◽  
Amino Acid Region ◽  
Rna Triphosphatase ◽  
Cycle Dependent

ABSTRACT Nuclear export of proteins containing leucine-rich nuclear export signals (NESs) is mediated by the NES receptor CRM1/Crm1p. We have carried out a yeast two-hybrid screen with Crm1p as a bait. The Crm1p-interacting clones were subscreened for nuclear export activity in a visual assay utilizing the Crm1p-inhibitor leptomycin B (LMB). This approach identified three Saccharomyces cerevisiaeproteins not previously known to have nuclear export activity. These proteins are the 5′ RNA triphosphatase Ctl1p, the cell cycle-regulated transcription factor Ace2p, and a protein encoded by the previously uncharacterized open reading frame YDR499W. Mutagenesis analysis show that YDR499Wp contains an NES that conforms to the consensus sequence for leucine-rich NESs. Mutagenesis of Ctl1p and Ace2p were unable to identify specific NES residues. However, a 29-amino-acid region of Ace2p, rich in hydrophobic residues, contains nuclear export activity. Ace2p accumulates in the nucleus at the end of mitosis and activates early-G1-specific genes. We now provide evidence that Ace2p is nuclear not only in late M-early G1 but also during other stages of the cell cycle. This feature of Ace2p localization explains its ability to activate genes such as CUP1, which are not expressed in a cell cycle-dependent manner.

scholarly journals The microtubule plus-end tracking protein Bik1 is required for chromosome congression

2021 ◽  
Author(s):  
Alexander Julner ◽  
Marjan Abbasi ◽  
Victoria Menendez Benito
Keyword(s):  
Cell Cycle ◽  
Nuclear Export ◽  
Cell Cycle Progression ◽  
Nuclear Export Signal ◽  
Microtubule Dynamics ◽  
Dependent Manner ◽  
Chromosome Congression ◽  
A Cell ◽  
Cycle Dependent ◽  
Export Signal

During mitosis, sister chromatids congress on either side of the spindle equator to facilitate the correct partitioning of the genomic material. Chromosome congression requires a finely tuned control of microtubule dynamics by the kinesin motor proteins. In Saccharomyces cerevisiae, the kinesin proteins Cin8, Kip1, and Kip3 have pivotal roles in chromosome congression. It has been hypothesized that additional proteins that modulate microtubule dynamics are also involved. Here, we show that the microtubule plus-end tracking protein Bik1 (the budding yeast ortholog of CLIP-170) is essential for chromosome congression. We find that nuclear Bik1 localizes to the kinetochores in a cell-cycle-dependent manner. Disrupting the nuclear pool of Bik1 with a nuclear export signal (Bik1-NES) leads to a slower cell cycle progression characterized by a delayed metaphase-anaphase transition. Bik1-NES cells have mispositioned kinetochores along the spindle in metaphase. Furthermore, using proximity-dependent methods, we identify Cin8 as an interaction partner of Bik1. Deleting CIN8 reduces the amount of Bik1 at the spindle. In contrast, Cin8 retains its typical bilobed distribution in Bik1-NES and does not localize to the unclustered kinetochores characteristic of Bik1-NES cells. Thus, we propose that Bik1 functions together with Cin8 to regulate kinetochore-microtubule dynamics for correct kinetochore positioning and chromosome congression.

scholarly journals Tumor suppressor role for myopodin in bladder cancer: loss of nuclear expression of myopodin is cell-cycle dependent and predicts clinical outcome

Oncogene ◽  
2003 ◽  
Vol 22 (34) ◽  
pp. 5298-5305 ◽  
Author(s):  
Marta Sanchez-Carbayo ◽  
Karin Schwarz ◽  
Elizabeth Charytonowicz ◽  
Carlos Cordon-Cardo ◽  
Peter Mundel
Keyword(s):  
Cell Cycle ◽  
Bladder Cancer ◽  
Tumor Suppressor ◽  
Clinical Outcome ◽  
Nuclear Expression ◽  
Cycle Dependent

scholarly journals Molecular Cloning and Cell Cycle-dependent Expression of Mammalian CRM1, a Protein Involved in Nuclear Export of Proteins

1997 ◽  
Vol 272 (47) ◽  
pp. 29742-29751 ◽  
Author(s):  
Nobuaki Kudo ◽  
Saadi Khochbin ◽  
Kazunori Nishi ◽  
Kazuaki Kitano ◽  
Mitsuhiro Yanagida ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Molecular Cloning ◽  
Nuclear Export ◽  
Cycle Dependent

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.

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