Casein kinase II inhibits the DNA-binding activity of Max homodimers but not Myc/Max heterodimers.

Berberich, S J; Cole, Michael

doi:10.1101/gad.6.2.166

Cited by 214 publications

(125 citation statements)

References 36 publications

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“…The signi®cance of this ®nding is unclear. However, a recent study suggests that phosphorylation of Max may inhibit binding of Max homodimers to DNA (Berberich and Cole, 1992), an e ect that might serve to block apoptosis (Zhang et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Scatter factor protects epithelial and carcinoma cells against apoptosis induced by DNA-damaging agents

et al. 1998

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Section: Discussionmentioning

confidence: 99%

Scatter factor protects epithelial and carcinoma cells against apoptosis induced by DNA-damaging agents

et al. 1998

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“…CKII-mediated phosphorylation of Max prevents Max homo-dimerization, whereas formation of Myc-Max hetero-dimers is not affected (21)(22)(23). Another case is the influence of phosphorylation on protein/DNA-binding interaction of many transcription factors i.e.…”

Section: Discussionmentioning

confidence: 99%

Insulin-activated Erk-mitogen-activated Protein Kinases Phosphorylate Sterol Regulatory Element-binding Protein-2 at Serine Residues 432 and 455 in Vivo

Kotzka

Lehr

Roth

et al. 2004

Journal of Biological Chemistry

102

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The transcription factor sterol regulatory element binding protein (SREBP)-2 plays a pivotal role in lipid metabolism. Previously, we have shown that the mature form of SREBP-2 is a substrate of Erk-mitogen-activated protein kinases (MAPK). The aim of the present study was to identify Erk-specific phosphorylation sites. Using a protein chemistry approach, we could identify Ser-432 and Ser-455 as major phosphorylation sites. Further characterization by electrophoretic mobility shift assay and promoter reporter gene analyses revealed that phosphorylation does not influence protein/DNA interaction, but enhances trans-activity. In intact cells, SREBP-2 is phosphorylated by insulin, which seems to be related to their bio-responses on low density lipoprotein receptor activity. These results suggest that activation of Erk-MAPK pathways by hormones such as insulin might be related to a novel regulatory principle of SREBP-2.Sterol regulatory element binding proteins (SREBPs) 1 are a family of basic helix-loop-helix transcription factors that are embedded as precursor proteins in the endoplasmic reticulum and nuclear envelope. To date, three SREBP isoforms have been detected: SREBP-1a, SREBP-1c (shorter splicing variant of SREBP-1a), as well as SREBP-2 (1-5). SREBP-2 is a major regulator of cholesterol homeostasis, whereas SREBP-1c regulates predominantly de novo synthesis of fatty acids. In contrast, SREBP-1a seems to influence both lipogenic and cholesterogenic enzymes (6).Activation of SREBPs initiated by cellular cholesterol depletion is mediated by sequential cleavage (7). As a result, the amino-terminal domain of the protein translocates into the nucleus and activates transcription of target genes. Beside this mechanism, which controls the abundance of activated SREBPs in the cell, we have demonstrated that trans-activity of the N-terminal domain of SREBPs is regulated directly by extra cellular stimuli, e.g. by hormones such as insulin (8, 9). Moreover, in these studies, we have shown that the N-terminal domains of SREBP-1a, SREBP-1c, and SREBP-2 are substrates of the extracellular signal-regulated kinase (Erk) subfamily of mitogen-activated protein kinases (MAPK). In this study, we have identified Ser-432 and Ser-455 as the major phosphorylation sites of Erk-MAPK in SREBP-2 using protein chemistry methodology. This phosphorylation has no influence on DNA interaction but affects trans-activity of SREBP-2. Accordingly, in cells, activation of low density lipoprotein (LDL) receptor gene by insulin is coupled to the identified Erk-specific phosphorylation sites in SREBP-2.

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“…For example, phosphorylation by CKII can have profound effects on the DNA-binding properties of the basic helixloop-helix proteins MYC and MAX. Whereas MAX homodimers and MYC/MAX heterodimers are able to bind to the same binding site when these proteins are unphosphorylated, DNA binding by MAX homodimers, but not MYC/MAX heterodimers, is sharply reduced by CKII phosphorylation (Berberich and Cole 1992). CKII has also been shown to phosphorylate the Drosophila homeodomain protein Engrailed (EN) during embryogenesis (Bourbon et al 1995).…”

Section: Ckii May Phosphorylate Antp In Vivomentioning

confidence: 99%

“…Phosphorylation by CKII has been reported to modulate the DNA-binding properties of several transcription factors (Manak et al 1990;Berberich and Cole 1992;Hupp et al 1992;Bourbon et al 1995). For example, phosphorylation by CKII can have profound effects on the DNA-binding properties of the basic helixloop-helix proteins MYC and MAX.…”

Section: Ckii May Phosphorylate Antp In Vivomentioning

confidence: 99%

A role for phosphorylation by casein kinase II in modulating Antennapedia activity in Drosophila.

Jaffe

Ryoo²,

Mann³

1997

Genes Dev.

114

101

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We present evidence that the in vivo activity of the HOX protein Antennapedia (ANTP) is modified because of phosphorylation by the serine/threonine kinase casein kinase II (CKII). Using an in vivo assay a form of ANTP that has alanine substitutions at its CKII target sites has, in addition to wild-type ANTP functions, the ability to alter severely thoracic and abdominal development. The novel functions of this protein suggest that this form of ANTP is not suppressed phenotypicaUy by the more posterior homeotic proteins. In contrast, the in vivo activity of a form of ANTP that contains acidic amino acid substitutions at its CKII target sites, thereby mimicking a constitutively phosphorylated ANTP protein, is greatly reduced. This hypoactive form of ANTP, but not the alanine-substituted form, is also reduced in its ability to bind to DNA cooperatively with the homeodomain protein Extradenticle. Our results suggest that phosphorylation of ANTP by CKII is important for preventing inappropriate activities of this homeotic protein during embryogenesis.

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Casein kinase II inhibits the DNA-binding activity of Max homodimers but not Myc/Max heterodimers.

Cited by 214 publications

References 36 publications

Scatter factor protects epithelial and carcinoma cells against apoptosis induced by DNA-damaging agents

Scatter factor protects epithelial and carcinoma cells against apoptosis induced by DNA-damaging agents

Insulin-activated Erk-mitogen-activated Protein Kinases Phosphorylate Sterol Regulatory Element-binding Protein-2 at Serine Residues 432 and 455 in Vivo

A role for phosphorylation by casein kinase II in modulating Antennapedia activity in Drosophila.

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