Identification of two residues in MCM5 critical for the assembly of MCM complexes and Stat1-mediated transcription activation in response to IFN-γ

DaFonseca, Christopher J.; Shu, Fong; Zhang, J. Jillian

doi:10.1073/pnas.061487598

Cited by 80 publications

(70 citation statements)

References 62 publications

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“…We have suggested previously that the function of the phosphoserine is to enhance the interaction of STAT TAD with other proteins, and the negative charge is important (23) perhaps through engaging positively charged residues on the interacting proteins (39). The negatively charged residue Asp has been shown to mimic the effects of many enzymes that require auto-Ser/Thr phosphorylation with varying degrees of efficiency (40,41).…”

Section: Discussionmentioning

confidence: 99%

The Conserved Leu-724 Residue Is Required for Both Serine Phosphorylation and Co-activator Recruitment for Stat1-mediated Transcription Activation in Response to Interferon-γ

Sun

Snyder

et al. 2005

Journal of Biological Chemistry

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The signal transducer and activator of transcription (STAT) proteins, a family of latent cytoplasmic transcription factors, become activated in response to extracellular ligand binding to cell surface receptors through tyrosine phosphorylation. Concurrently, a serine phosphorylation event in the transcription activation domain (serine 727 for Stat1) occurs. This serine phosphorylation is essential for the maximal transcription activity of Stat1. Here we show that, in addition to the Ser-727 residue and its phosphorylation, the conserved Leu-724 residue is also essential for gene activation mediated by Stat1. When Leu-724 is mutated to Ala, phosphorylation of Stat1 Ser-727 is defective both in vivo and in vitro. Surprisingly, we found a StatL724I mutant that lacks transcription activity despite normal Ser-727 phosphorylation. Further analyses show that Leu-724, as well as the phospho-Ser-727, are essential for the recruitment of the transcription co-activator CBP/p300 to the promoters of Stat1 target genes. Our results demonstrate that the conserved Leu-724 residue is a key residue that controls the maximal transcription activities of Stat1 in IFN-␥ signaling.

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Section: Discussionmentioning

confidence: 99%

The Conserved Leu-724 Residue Is Required for Both Serine Phosphorylation and Co-activator Recruitment for Stat1-mediated Transcription Activation in Response to Interferon-γ

Sun

Snyder

et al. 2005

Journal of Biological Chemistry

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“…Several lines of evidence suggest that the MCM proteins associate with specific transcription factors. During biochemical purification, the Mcm3-Mcm5 heterodimer associates with STAT1␣, a transcription factor stimulated by gamma interferon (50,359). This association is mediated by Mcm5.…”

Section: Transcriptionmentioning

confidence: 99%

Eukaryotic MCM Proteins: Beyond Replication Initiation

Forsburg

2004

Microbiol Mol Biol Rev

493

506

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The minichromosome maintenance (or MCM) protein family is composed of six related proteins that are conserved in all eukaryotes. They were first identified by genetic screens in yeast and subsequently analyzed in other experimental systems using molecular and biochemical methods. Early data led to the identification of MCMs as central players in the initiation of DNA replication. More recent studies have shown that MCM proteins also function in replication elongation, probably as a DNA helicase. This is consistent with structural analysis showing that the proteins interact together in a heterohexameric ring. However, MCMs are strikingly abundant and far exceed the stoichiometry of replication origins; they are widely distributed on unreplicated chromatin. Analysis of mcm mutant phenotypes and interactions with other factors have now implicated the MCM proteins in other chromosome transactions including damage response, transcription, and chromatin structure. These experiments indicate that the MCMs are central players in many aspects of genome stability

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“…The equivalent cysteine residue in human MCM5, C172, was therefore mutated to tyrosine (C172Y) and examined for binding to MCM3. Multiple studies show that MCM5 and MCM3 exist as a tightly associated dimer that can easily be isolated from other MCMs (Bochman et al, 2008;DaFonseca et al, 2001). Therefore, binding to MCM3 reflects binding to all family members.…”

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confidence: 99%

The cyclin A centrosomal localization sequence recruits MCM5 and Orc1 to regulate centrosome reduplication

Ferguson

Pascreau

Maller

2010

Journal of Cell Science

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SummaryCentrosomes are the major microtubule-organizing centers in animal cells and regulate formation of a bipolar mitotic spindle. Aberrant centrosome number causes chromosome mis-segregation, and has been implicated in genomic instability and tumor development. Previous studies have demonstrated a role for the DNA replication factors MCM5 and Orc1 in preventing centrosome reduplication. Cyclin A-Cdk2 localizes on centrosomes by means of a modular centrosomal localization sequence (CLS) that is distinct from that of cyclin E. Here, we show that cyclin A interacts with both MCM5 and Orc1 in a CLS-dependent but Cdk-independent manner. Although the MRAIL hydrophobic patch is contained within the cyclin A CLS, binding of both MCM5 and Orc1 to cyclin A does not require a wild-type hydrophobic patch. The same domain in MCM5 that mediates interaction with cyclin E also binds cyclin A, resulting in centrosomal localization of MCM5. Finally, unlike its function in DNA synthesis, MCM5-mediated inhibition of centrosome reduplication in S-phase-arrested CHO cells does not require binding to other MCM family members. These results suggest that cyclins E and A sequentially prevent centrosome reduplication throughout interphase by recruitment of DNA replication factors such as MCM5 and Orc1.

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Identification of two residues in MCM5 critical for the assembly of MCM complexes and Stat1-mediated transcription activation in response to IFN-γ

Cited by 80 publications

References 62 publications

The Conserved Leu-724 Residue Is Required for Both Serine Phosphorylation and Co-activator Recruitment for Stat1-mediated Transcription Activation in Response to Interferon-γ

The Conserved Leu-724 Residue Is Required for Both Serine Phosphorylation and Co-activator Recruitment for Stat1-mediated Transcription Activation in Response to Interferon-γ

Eukaryotic MCM Proteins: Beyond Replication Initiation

The cyclin A centrosomal localization sequence recruits MCM5 and Orc1 to regulate centrosome reduplication

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