M-Phase-Specific Phosphorylation of the POU Transcription Factor GHF-1 by a Cell Cycle-Regulated Protein Kinase Inhibits DNA Binding

Caelles, Carmé; Hennemann, Hanjo; Karin, Michael

doi:10.1128/mcb.15.12.6694

Cited by 61 publications

(63 citation statements)

References 40 publications

(77 reference statements)

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“…The phosphoacceptor residue, Thr-220 is located into the POU homeodomain. These results could not be confirmed in cultured cells (58). However, the Thr-220 is transiently phosphorylated during mitosis by a mitosis-specific kinase.…”

Section: Autoregulation Of Human Pit1/ghf1 Gene Expression-contrasting

confidence: 43%

“…However, the Thr-220 is transiently phosphorylated during mitosis by a mitosis-specific kinase. This results in a transient decrease of the Pit-1/GHF-1 DNA binding activity during the M phase of the cell cycle (58). Therefore, a possible function for the TRE could be to mediate a complete transcriptional shut-off of the human PIT1/GHF1 gene when the DNA binding activity of the Pit-1/GHF-1 protein is inhibited by mitotic phosphorylation.…”

Section: Autoregulation Of Human Pit1/ghf1 Gene Expression-mentioning

confidence: 99%

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AP-1 and Oct-1 Transcription Factors Down-regulate the Expression of the Human PIT1/GHF1 Gene

Delhase

Castrillo

Hoya

et al. 1996

Journal of Biological Chemistry

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The pituitary-specific transcription factor Pit-1/ GHF-1 is a member of the POU domain family of regulatory proteins. It is involved in the commitment and expansion of the somatotropic cell lineage and activates the transcription of a set of anterior pituitary genes. We have cloned the human PIT1/GHF1 gene and characterized the regulatory mechanisms controlling its promoter activation and regulation. A minimal promoter region (؊102 to ؉15) contains the cis-acting elements that confer to the human PIT1/GHF1 gene a high basal transcriptional activity, the tissue-specific expression, and the autoregulation by Pit-1/GHF-1 protein. The upstream promoter region contains a multiplicity of Pit-1/ GHF-1 binding sites that do not show any synergistic interaction with the minimal promoter. The transcriptional activity is negatively regulated by Oct-1 and mediated by an octamer-binding site (OTF). In addition, we have also identified a 12-O-tetradecanoylphorbol-13-acetate-responsive element, which overlaps with a Pit-1/ GHF-1 binding site. A mutually exclusive binding of the activator protein-1 (AP-1) and Pit-1/GHF-1 has been observed on this composite site, and AP-1 was shown to down-regulate PIT1/GHF1 transcription.

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Section: Autoregulation Of Human Pit1/ghf1 Gene Expression-contrasting

confidence: 43%

Section: Autoregulation Of Human Pit1/ghf1 Gene Expression-mentioning

confidence: 99%

AP-1 and Oct-1 Transcription Factors Down-regulate the Expression of the Human PIT1/GHF1 Gene

Delhase

Castrillo

Hoya

et al. 1996

Journal of Biological Chemistry

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“…Among this family, Ikaros and Sp1 are not only excluded from chromatin in early mitosis, but it has also been shown that the three linkers of Ikaros and at least one of the Sp1 linkers are phosphorylated [Dovat et al, 2002]. Similarly, the DNA-binding ability of Oct-1 and GHF-1, two members of the POU family, is lost upon mitotic phosphorylation of the same conserved amino acid of the POU domain [Segil et al, 1991;Caelles et al, 1995]. These findings imply that mitotic inactivation of transcription factors through phosphorylation may be a mechanism common to every family of transcription factors.…”

Section: Spatial Mitotic Reorganization Exclusion Of Transcription-asmentioning

confidence: 98%

Mitotic partitioning of transcription factors

Delcuve

Davie

2008

J of Cellular Biochemistry

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Mitosis is a highly orchestrated process involving numerous protein kinases and phosphatases. At the onset of mitosis, the chromatin condensation into metaphase chromosomes is correlated with global phosphorylation of histone H3. The bulk of transcription is silenced while many of the transcription-associated proteins, including transcription and chromatin remodeling factors, are excluded from chromatin, typically as a consequence of their phosphorylation. Components of the transcription machinery and regulatory proteins are recycled and equally partitioned between newly divided cells by mechanisms that may involve microtubules, microfilaments or intermediate filaments.However, as demonstrated in the case of Runx2, a subset of transcription factors involved in lineage-specific control, likely remain associated with their target genes to direct the deposition or removal of epigenetic marks. The displacement and re-entry into daughter cells of transcription and chromatin remodeling factors are temporally defined and regulated. Reformation of daughter nuclei is a critical time to reestablish the proper gene expression pattern. The mechanisms involved in the marking and re-establishment of gene expression has been elucidated for few genes. The elucidation of how the memory of a programmed expression profile is transmitted to daughter cells represents a challenge. J. Cell. Biochem. 105: 1-8, 2008. ß 2008 Wiley-Liss, Inc. KEY WORDS: MITOSIS; GENE EXPRESSION; EPIGENETIC MARKS; TRANSCRIPTION FACTORS; CHROMATIN REMODELING; PHOSPHORYLATIONA t the onset of mitosis, while chromosome condensation takes place to facilitate segregation of sister chromatids between daughter cells, the nuclear envelope ruptures and the bulk of transcription activity ceases. The entry into mitosis is also characterized by extensive protein phosphorylation. The condensation of interphase chromatin into mitotic chromosomes, restricting the accessibility of DNA to transcription factors and RNA polymerases, has been put forward as the most evident mechanism of transcription shut-down [Gottesfeld and Forbes, 1997]. However, on and off exchanges of transcription factors and nucleosome components were observed from condensed mitotic chromosomes, suggesting that transcription arrest is due to reasons other than chromatin condensation itself [Chen et al., 2005]. Alternative mechanisms include inactivation by phosphorylation and/or displacement of RNA polymerases, chromatin remodeling complexes and transcription factors from mitotic chromosomes [Gottesfeld and Forbes, 1997;John and Workman, 1998]. When cells exit mitosis, specific gene expression patterns must be reestablished. It has been proposed that a subset of factors act as molecular bookmarks by binding to mitotic chromatin, as genes poised for reactivation are marked by protein-dependent structural distortions [Michelotti et al., 1997]. Several studies providing evidence to support this hypothesis are reviewed here. Furthermore, the elucidation of the spatial and temporal mitotic reorganiza...

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“…Although the mechanism for Ras stimulation of the Pit-1 R2 TAD has yet to be elucidated, we know that in Ets-1 the Thr-82 MAP kinase phosphorylation site is required for Ras responsiveness because mutation of this site to an alanine blocks the ability of Ets-1 to enhance the Ras response (10,14). There are potential phosphorylation sites within the Pit-1 TAD, but none of them is a proline-directed MAP kinase site, and to date only serine 115 and threonines 219 and 220 have been shown to be phosphorylated by various signaling pathways and kinases (47,48), suggesting that Ras activation of the amino-terminal Pit-1 TAD is not mediated through direct phosphorylation of the TAD. Thus, the R2 subregion represents a novel and tissuespecific Ras-regulated TAD.…”

Section: Pit-1 Monomer Versus Dimer Dna Binding Sites Are Not a Primamentioning

confidence: 99%

Ras Signaling and Transcriptional Synergy at a Flexible Ets-1/Pit-1 Composite DNA Element Is Defined by the Assembly of Selective Activation Domains

Duval

Jean

Gutierrez‐Hartmann

2003

Journal of Biological Chemistry

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Pit-1 and Ets-1 binding to a composite element synergistically activates and targets Ras-mitogen-activated protein kinase signaling to the rat prolactin promoter. These transcriptional responses appear to depend on three molecular features: organization of the Ets-1/Pit-1 composite element, physical interaction of these two factors via the Pit-1 homeodomain (amino acids 199 -291) and the Ets-1 regulatory III domain (amino acids 190 -257), and assembly of their transcriptional activation domains (TADs). Here we show that the organization of the Ets-1/Pit-1 composite element tolerates significant flexibility with regard to Ras stimulation and synergy. Specifically, the putative monomeric Pit-1 binding site can be substituted with bona fide binding sites for either a Pit-1 monomer or dimer, and these sites tolerated a separation of 28 bp. Additionally, we show that the physical interaction of Ets-1 and Pit-1 is not required for Ras responsiveness or synergy because block mutations of the Pit-1 interaction surface in Ets-1, which reduced Ets-1/Pit-1 binding in vitro, did not significantly affect Ets-1 stimulation of Ras responsiveness or synergy. We also show differential use of distinct TAD subtypes and Pit-1 TAD subregions to mediate either synergy or Ras responsiveness. Specifically, TADs from Gal4, VP16, or Ets-2 regulatory III domain linked to Ets-1 DNA binding domain constructs restored synergy to these TAD/Ets-1 DNA binding domain fusions. Conversely, deletion of the defined Pit-1 TAD (amino acids 2-80) retained synergy, but not Ras responsiveness. Consequently, we further defined the Pit-1 amino-terminal TAD into region 1 (R1, amino acids 2-45) and region 2 (R2, amino acids 46 -80). R1 appears to regulate basal and synergistic responses, whereas the Ras response was mapped to R2. In summary, Ras responsiveness and Pit-1/Ets-1 synergy are mediated through the assembly of distinct TADs at a flexible composite element, indicating that different mechanisms underlie these two transcriptional responses and that the Pit-1 R2 subregion represents a novel, tissue-specific Ras-responsive TAD.

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M-Phase-Specific Phosphorylation of the POU Transcription Factor GHF-1 by a Cell Cycle-Regulated Protein Kinase Inhibits DNA Binding

Cited by 61 publications

References 40 publications

AP-1 and Oct-1 Transcription Factors Down-regulate the Expression of the Human PIT1/GHF1 Gene

AP-1 and Oct-1 Transcription Factors Down-regulate the Expression of the Human PIT1/GHF1 Gene

Mitotic partitioning of transcription factors

Ras Signaling and Transcriptional Synergy at a Flexible Ets-1/Pit-1 Composite DNA Element Is Defined by the Assembly of Selective Activation Domains

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