Conserved cysteine residues of Oct-2 POU domain confer sensitivity to oxidation but are dispensable for sequence-specific DNA binding

Rigoni, Patrick; Xu, Licen; Harshman, Keith; Schaffner, Walter; Arnosti, David N.

doi:10.1016/0167-4781(93)90174-c

Cited by 15 publications

(7 citation statements)

References 34 publications

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“…Furthermore activity of a reporter construct regulated by an OCT4 responsive element was increased upon co‐transfection of OCT4 and thioredoxin expression vectors compared with OCT4 alone (Guo et al., 2004). DNA binding of the OCT2 protein had earlier also been reported to be reversibly inhibited by oxidation (Rigoni et al., 1993).…”

Section: Mechanisms Regulating Pou Protein Dna Binding and Transactivmentioning

confidence: 99%

POU domain transcription factors: BRN2 as a regulator of melanocytic growth and tumourigenesis

Cook

Sturm

2008

Pigment Cell Melanoma Res

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SummarySeveral parallels between stem cell biology and tumour behaviour have been discovered in recent times. Such commonality is apparent in the unlimited capacity for cell division together with the lack of a differentiated phenotype in embryonic and adult stem cells, traits shared with tumour cells. Differentiation is a tightly regulated process that is mediated by the actions of multiple transcription factor families. The POU domaincontaining family of transcription factors contains multiple mammalian members divided into six classes, which can be expressed broadly or in a cell-specific manner, and which are regulators of cell fate decisions of many different lineages. Target gene regulation can occur via a POU factor acting alone, or in combination with other POU proteins, ubiquitous co-activators or co-repressors, or other lineage restricted transcription factors. Aberrant levels of POU proteins have been found in several malignancies, including melanoma, connecting the otherwise developmentally restricted gene regulatory functions of POU transcription factors to the critical determinants of malignant transformation. Here, we focus on the role of the BRN2 (POU3F2/ N-Oct-3) transcription factor in the melanocytic lineage where it may co-ordinate normal developmental cues that can be re-activated in melanoma. Recent studies have shown BRN2 to be responsive to MAPK pathway activation and to modulate the levels of MITF so as to suppress the differentiated melanocytic phenotype and to enhance tumour metastasis.

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Section: Mechanisms Regulating Pou Protein Dna Binding and Transactivmentioning

confidence: 99%

POU domain transcription factors: BRN2 as a regulator of melanocytic growth and tumourigenesis

Cook

Sturm

2008

Pigment Cell Melanoma Res

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“…42 In POU proteins, only a few amino acid residues have been identified as being modified after protein translation. For instance, Jun kinase phosphorylates two residues in the POU domain of POU6f1 but these amino acids are not conserved in the other POU proteins except in POU6f2.…”

Section: Discussionmentioning

confidence: 99%

Differential Effects of Phosphorylation on DNA Binding Properties of N Oct-3 Are Dictated by Protein/DNA Complex Structures

Nieto

Joseph

Stella

et al. 2007

Journal of Molecular Biology

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“…When NFI is bound to DNA, it is partially protected against oxidation. Several DNA binding domains, of which the structure is known, contain cysteine residues with similar properties, and in all of these cases this cysteine is very close to the DNA, e.g., NF-B/rel (29), Myb (19), p53 (20,23), c-fos and c-jun (1,4), or even makes specific base contacts, as in the case of the bovine papillomavirus E2 protein (22,30) and the POU homeodomain (25,41). Furthermore, the region around this cysteine residue in NFI is the only continuous stretch of amino acids that is more than 95% identical to the C. elegans NFI, as predicted from the genomic sequence identified in the C. elegans genome sequencing project.…”

Section: Discussionmentioning

confidence: 99%

Two Regions within the DNA Binding Domain of Nuclear Factor I Interact with DNA and Stimulate Adenovirus DNA Replication Independently

Dekker

Oosterhout

Vliet

1996

Molecular and Cellular Biology

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The cellular transcription factor nuclear factor I (NFI) stimulates adenovirus DNA replication by up to 50-fold. The NFI DNA binding domain (NFI-BD) is sufficient for stimulation and interacts with the viral DNA polymerase, thereby recruiting the precursor terminal protein-DNA polymerase complex (pTP-pol) to the origin of replication. The mechanism of DNA binding by NFI is unknown. To examine DNA binding and stimulation of adenovirus DNA replication by NFI-BD in more detail, we generated a series of deletion mutants and show that the DNA binding domain of NFI consists of two subdomains: a highly basic N-terminal domain that binds nonspecifically to DNA and a C-terminal domain that binds specifically but with very low affinity to the NFI recognition site. Both of these subdomains stimulate DNA replication, although not to the same extent as the intact DNA binding domain. The N-terminal domain has an alpha-helical structure, as shown by circular dichroism spectroscopy. The C-terminal domain interacts with the pTP-pol complex and is able to recruit the pTP-pol complex to DNA, which leads to pTP-pol-dependent stimulation of replication. The N-terminal domain also stimulates replication in a pTP-pol-dependent manner and enhances binding of pTP-pol to DNA. Since we could not detect a direct protein-protein interaction between pTP-pol and the N-terminal domain, we suggest that this domain stimulates replication by inducing structural changes in the DNA.

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Conserved cysteine residues of Oct-2 POU domain confer sensitivity to oxidation but are dispensable for sequence-specific DNA binding

Cited by 15 publications

References 34 publications

POU domain transcription factors: BRN2 as a regulator of melanocytic growth and tumourigenesis

POU domain transcription factors: BRN2 as a regulator of melanocytic growth and tumourigenesis

Differential Effects of Phosphorylation on DNA Binding Properties of N Oct-3 Are Dictated by Protein/DNA Complex Structures

Two Regions within the DNA Binding Domain of Nuclear Factor I Interact with DNA and Stimulate Adenovirus DNA Replication Independently

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