scholarly journals Cell Cycle-dependent Regulation of the Forkhead Transcription Factor FOXK2 by CDK·Cyclin Complexes

2010 ◽  
Vol 285 (46) ◽  
pp. 35728-35739 ◽  
Author(s):  
Anett Marais ◽  
Zongling Ji ◽  
Emma S. Child ◽  
Eberhard Krause ◽  
David J. Mann ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Transcription Factor ◽  
Forkhead Transcription Factor ◽  
Cycle Dependent

scholarly journals Regulation of Cell Cycle-Specific Gene Expression through Cyclin-Dependent Kinase-Mediated Phosphorylation of the Forkhead Transcription Factor Fkh2p

2004 ◽  
Vol 24 (22) ◽  
pp. 10036-10046 ◽  
Author(s):  
Aline Pic-Taylor ◽  
Zoulfia Darieva ◽  
Brian A. Morgan ◽  
Andrew D. Sharrocks
Keyword(s):  
Cell Cycle ◽  
Transcription Factor ◽  
Specific Gene ◽  
Cyclin Dependent Kinase ◽  
Forkhead Transcription Factor ◽  
Cyclin Dependent Kinases ◽  
Regulated Expression ◽  
Dependent Protein ◽  
Cycle Dependent ◽  
Regulation Of Cell Cycle

ABSTRACT The forkhead transcription factor Fkh2p acts in a DNA-bound complex with Mcm1p and the coactivator Ndd1p to regulate cell cycle-dependent expression of the CLB2 gene cluster in Saccharomyces cerevisiae. Here, we demonstrate that Fkh2p is a target of cyclin-dependent protein kinases and that phosphorylation of Fkh2p promotes interactions between Fkh2p and the coactivator Ndd1p. These phosphorylation-dependent changes in the Fkh2p-Ndd1p complex play an important role in the cell cycle-regulated expression of the CLB2 cluster. Our data therefore identify an important regulatory target for cyclin-dependent kinases in the cell cycle and further our molecular understanding of the key cell cycle regulatory transcription factor Fkh2p.

scholarly journals Forkhead Transcription Factor FoxM1 Regulates Mitotic Entry and Prevents Spindle Defects in Cerebellar Granule Neuron Precursors

2007 ◽  
Vol 27 (23) ◽  
pp. 8259-8270 ◽  
Author(s):  
Ulrich Schüller ◽  
Qing Zhao ◽  
Susana A. Godinho ◽  
Vivi M. Heine ◽  
René H. Medema ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Transcription Factor ◽  
Target Genes ◽  
Cyclin B1 ◽  
Null Alleles ◽  
Cerebellar Granule Neuron ◽  
Forkhead Transcription Factor ◽  
Cerebellar Granule ◽  
Granule Neuron ◽  
Granule Neuron Precursors

ABSTRACT The forkhead transcription factor FoxM1 has been reported to regulate, variously, proliferation and/or spindle formation during the G2/M transition of the cell cycle. Here we define specific functions of FoxM1 during brain development by the investigation of FoxM1 loss-of-function mutations in the context of Sonic hedgehog (Shh)-induced neuroproliferation in cerebellar granule neuron precursors (CGNP). We show that FoxM1 is expressed in the cerebellar anlagen as well as in postnatal proliferating CGNP and that it is upregulated in response to activated Shh signaling. To determine the requirements for FoxM1 function, we used transgenic mice carrying conventional null alleles or conditionally targeted alleles in conjunction with specific Cre recombinase expression in CGNP or early neural precursors driven by Math1 or Nestin enhancers. Although the overall cerebellar morphology was grossly normal, we observed that the entry into mitosis was postponed both in vivo and in Shh-treated CGNP cultures. Cell cycle analysis and immunohistochemistry with antibodies against phosphorylated histone H3 indicated a significant delay in the G2/M transition. Consistent with this, FoxM1-deficient CGNP showed decreased levels of the cyclin B1 and Cdc25b proteins. Furthermore, the loss of FoxM1 resulted in spindle defects and centrosome amplification. These findings indicate that the functions of FoxM1 in Shh-induced neuroproliferation are restricted to the regulation of the G2/M transition in CGNP, most probably through transcriptional effects on target genes such as those coding for B-type cyclins.

scholarly journals Ste12 and Mcm1 regulate cell cycle-dependent transcription of FAR1.

1996 ◽  
Vol 16 (6) ◽  
pp. 2830-2837 ◽  
Author(s):  
L J Oehlen ◽  
J D McKinney ◽  
F R Cross
Keyword(s):  
Cell Cycle ◽  
Transcription Factor ◽  
Transcriptional Activation ◽  
G1 Phase ◽  
Protein Accumulation ◽  
Transcriptional Activation Domain ◽  
Cycle Arrest ◽  
Gal1 Promoter ◽  
Combinatorial Control ◽  
Cycle Dependent

The transcripts of many genes involved in Saccharomyces cerevisiae mating were found to fluctuate during the cell cycle. In the absence of a functional Ste12 transcription factor, both the levels and the cell cycle pattern of expression of these genes were affected. FUS1 and AGA1 levels, which are maximally expressed only in G1-phase cells, were strongly reduced in ste12- cells. The cell cycle transcription pattern for FAR1 was changed in ste12- cells: the gene was still significantly expressed in G2/M, but transcript levels were strongly reduced in G1 phase, resulting in a lack of Far1 protein accumulation. G2/M transcription of FAR1 was dependent on the transcription factor Mcm1, and expression of a gene with Mcm1 fused to a strong transcriptional activation domain resulted in increased levels of FAR1 transcription. The pattern of cell cycle-regulated transcription of FAR1 could involve combinatorial control of Ste12 and Mcm1. Forced G1 expression of FAR1 from the GAL1 promoter resorted the ability to arrest in response to pheromone in ste12-cells. This indicates that transcription of FAR1 in the G1 phase is essential for accumulation of the protein and for pheromone-induced cell cycle arrest.

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 Protein Kinase SGK Mediates Survival Signals by Phosphorylating the Forkhead Transcription Factor FKHRL1 (FOXO3a)

2001 ◽  
Vol 21 (3) ◽  
pp. 952-965 ◽  
Author(s):  
Anne Brunet ◽  
Jongsun Park ◽  
Hien Tran ◽  
Linda S. Hu ◽  
Brian A. Hemmings ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Cell Survival ◽  
Cell Cycle Progression ◽  
Target Genes ◽  
Cellular Functions ◽  
Forkhead Transcription Factor ◽  
Pi3k Activation ◽  
Phosphoinositide 3 Kinase

ABSTRACT Serum- and glucocorticoid-inducible kinases (SGKs) form a novel family of serine/threonine kinases that are activated in response to a variety of extracellular stimuli. SGKs are related to Akt (also called PKB), a serine/threonine kinase that plays a crucial role in promoting cell survival. Like Akt, SGKs are activated by the phosphoinositide-3 kinase (PI3K) and translocate to the nucleus upon growth factor stimulation. However the physiological substrates and cellular functions of SGKs remained to be identified. We hypothesized that SGKs regulate cellular functions in concert with Akt by phosphorylating common targets within the nucleus. The best-characterized nuclear substrates of Akt are transcription factors of the Forkhead family. Akt phosphorylates Forkhead transcription factors such as FKHRL1, leading to FKHRL1's exit from the nucleus and the consequent shutoff of FKHRL1 target genes. We show here that SGK1, like Akt, promotes cell survival and that it does so in part by phosphorylating and inactivating FKHRL1. However, SGK and Akt display differences with respect to the efficacy with which they phosphorylate the three regulatory sites on FKHRL1. While both kinases can phosphorylate Thr-32, SGK displays a marked preference for Ser-315 whereas Akt favors Ser-253. These findings suggest that SGK and Akt may coordinately regulate the function of FKHRL1 by phosphorylating this transcription factor at distinct sites. The efficient phosphorylation of these three sites on FKHRL1 by SGK and Akt appears to be critical to the ability of growth factors to suppress FKHRL1-dependent transcription, thereby preventing FKHRL1 from inducing cell cycle arrest and apoptosis. These findings indicate that SGK acts in concert with Akt to propagate the effects of PI3K activation within the nucleus and to mediate the biological outputs of PI3K signaling, including cell survival and cell cycle progression.

scholarly journals Forkhead transcription factor Fkh1: insights into functional regulatory domains crucial for recruitment of Sin3 histone deacetylase complex

2021 ◽  
Author(s):  
Rasha Aref ◽  
Marwa N. M. E. Sanad ◽  
Hans-Joachim Schüller
Keyword(s):  
Cell Cycle ◽  
Amino Acids ◽  
Transcription Factor ◽  
Transcriptional Repression ◽  
Histone Deacetylases ◽  
Cell Cycle Control ◽  
Forkhead Transcription Factor ◽  
Specific Domain ◽  
Cell Cycle Genes ◽  
Chromatin Architecture

AbstractTranscription factors are inextricably linked with histone deacetylases leading to compact chromatin. The Forkhead transcription factor Fkh1 is mainly a negative transcriptional regulator which affects cell cycle control, silencing of mating-type cassettes and induction of pseudohyphal growth in the yeast Saccharomyces cerevisiae. Markedly, Fkh1 impinges chromatin architecture by recruiting large regulatory complexes. Implication of Fkh1 with transcriptional corepressor complexes remains largely unexplored. In this work we show that Fkh1 directly recruits corepressors Sin3 and Tup1 (but not Cyc8), providing evidence for its influence on epigenetic regulation. We also identified the specific domain of Fkh1 mediating Sin3 recruitment and substantiated that amino acids 51–125 of Fkh1 bind PAH2 of Sin3. Importantly, this part of Fkh1 overlaps with its Forkhead-associated domain (FHA). To analyse this domain in more detail, selected amino acids were replaced by alanine, revealing that hydrophobic amino acids L74 and I78 are important for Fkh1-Sin3 binding. In addition, we could prove Fkh1 recruitment to promoters of cell cycle genes CLB2 and SWI5. Notably, Sin3 is also recruited to these promoters but only in the presence of functional Fkh1. Our results disclose that recruitment of Sin3 to Fkh1 requires precisely positioned Fkh1/Sin3 binding sites which provide an extended view on the genetic control of cell cycle genes CLB2 and SWI5 and the mechanism of transcriptional repression by modulation of chromatin architecture at the G2/M transition.

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