Identification of Pirin, a Novel Highly Conserved Nuclear Protein

Wendler, Wolfgang; Kremmer, Elisabeth; Förster, Reinhold; Winnacker, Ernst‐Ludwig

doi:10.1074/jbc.272.13.8482

Cited by 116 publications

(140 citation statements)

References 43 publications

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“…They included Tat-interacting protein Tip60; Pirin, a potential co-factor of nuclear factor I; Bard1, known to functionally interact with the tumor suppressor Brca1 and Jab1, which interacts with the transactivation domain of c-Jun (Claret et al, 1996;Kamine et al, 1996;Wendler et al, 1997;Wu et al, 1996). The only common properties of the identi®ed factors is that they are nuclear proteins and associate with gene regulators.…”

Section: Various Nuclear Co-factors Interact With Bcl-3mentioning

confidence: 99%

“…Pirin, which most e ciently formed complexes with Bcl-3 and p50 bound to DNA, has originally been isolated as a nuclear factor I (NFI) associated protein (Wendler et al, 1997). It is predominantly present in nuclear dot-like structures and is devoid of known motifs, except for distant similarities with prokaryotic and yeast proteins of yet unknown function.…”

Section: Various Nuclear Co-factors Interact With Bcl-3mentioning

confidence: 99%

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The Bcl-3 oncoprotein acts as a bridging factor between NF-κB/Rel and nuclear co-regulators

et al. 1999

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The proto-oncoprotein Bcl-3 is a member of the IkB family and is present predominantly in the nucleus. To gain insight into speci®c nuclear functions of Bcl-3 we have isolated proteins that interact with its ankyrin repeat domain. Using the yeast two-hybrid-system we identi®ed four novel binding partners of Bcl-3 in addition to NF-kB p50 and p52, previously known to associate with Bcl-3. The novel Bcl-3 interactors Jab1, Pirin, Tip60 and Bard1 are nuclear proteins which also bind to other transcription factors including c-Jun, nuclear factor I (NFI), HIV-1 Tat or the tumor suppressor and Polll holoenzyme component Brca1, respectively. Bcl-3, p50, and either Bard1, Tip60 or Pirin are sequestered into quarternary complexes on NF-kB DNA binding sites, whereas Jab1 enhances p50-Bcl-3-DNA complex formation. Furthermore, the histone acetylase Tip60 enhances Bcl-3-p50 activated transcription through an NF-kB binding site, indicating that quarternary complexes containing Bcl-3 interactors modulate NF-kB driven gene expression. These data implicate Bcl-3 as an adaptor between NF-kB p50/p52 and other transcription regulators and suggest that its gene activation function may at least in part be due to recruitment of the Tip60 histone actetylase.

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Section: Various Nuclear Co-factors Interact With Bcl-3mentioning

confidence: 99%

Section: Various Nuclear Co-factors Interact With Bcl-3mentioning

confidence: 99%

The Bcl-3 oncoprotein acts as a bridging factor between NF-κB/Rel and nuclear co-regulators

et al. 1999

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“…13 Pirin (PIR) is a highly conserved nuclear protein belonging to the Cupin superfamily 14 whose function is, to date, poorly characterized. It has been described as a putative transcriptional regulator on the basis of its physical association with the nuclear I/CCAAT box transcription factor NFI/CTF1 15 and with the B-cell lymphoma protein, BCL-3, a regulator of NF-B/Rel activity. A recent report shows that PIR controls melanoma cell migration through the transcriptional regulation of snail homolog 2, SNAI2 (previously SLUG).…”

mentioning

confidence: 99%

Pirin Inhibits Cellular Senescence in Melanocytic Cells

Licciulli

Luise

Scafetta

et al. 2011

The American Journal of Pathology

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Cellular senescence has been widely recognized as a tumor suppressing mechanism that acts as a barrier to cancer development after oncogenic stimuli. A prominent in vivo model of the senescence barrier is represented by nevi, which are composed of melanocytes that, after an initial phase of proliferation induced by activated oncogenes (most commonly BRAF), are blocked in a state of cellular senescence. Transformation to melanoma occurs when genes involved in controlling senescence are mutated or silenced and cells reacquire the capacity to proliferate. Pirin (PIR) is a highly conserved nuclear protein that likely functions as a transcriptional regulator whose expression levels are altered in different types of tumors. We analyzed the expression pattern of PIR in adult human tissues and found that it is expressed in melanocytes and has a complex pattern of regulation in nevi and melanoma: it is rarely detected in mature nevi, but is expressed at high levels in a subset of melanomas. Loss of function and overexpression experiments in normal and transformed melanocytic cells revealed that PIR is involved in the negative control of cellular senescence and that its expression is necessary to overcome the senescence barrier. Our results suggest that PIR may have a relevant role in melanoma progression.

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“…It has been defined as a transcriptional regulator on the basis of its interaction with B-cell chronic lymphocytic leukemia/lymphoma 3 5 and nuclear factor I/CCAAT box transcription factor. 4 We therefore analyzed the transcriptional effects of PIR silencing in U937 cells and did not detect modulation of genes associated with myeloid differentiation. Although this may be due to the cellular model under analysis, expression of AML1/ETO or PML/RAR in the same model system does indeed result in repression of essential regulators of myeloid differentiation, such as genes encoding for the PU.1 and CEBP family of transcriptional regulators.…”

Section: Discussionmentioning

confidence: 99%

“…4 Although its function has not been fully elucidated, a role for PIR in transcriptional regulation has been proposed on the basis of its interaction with nuclear factor I/CCAAT box transcription factor as well as with the protooncoprotein B-cell chronic lymphocytic leukemia/lymphoma 3, 5 a member of the IkB family that modulates the activities of nuclear factor (NF)-kB/Rel transcription factors. 6 PIR is a member of the functionally diverse cupin family of proteins, 7 and has been shown to possess quercetinase enzymatic activity.…”

Section: Introductionmentioning

confidence: 99%

Pirin downregulation is a feature of AML and leads to impairment of terminal myeloid differentiation

et al. 2009

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Terminal differentiation of blood cells requires the concerted action of a series of transcription factors that are expressed at specific stages of maturation and function in a cell-type and dosage-dependent manner. Leukemogenic oncoproteins block differentiation by subverting the normal transcriptional status of hematopoietic precursor cells. Pirin (PIR) is a putative transcriptional regulator whose expression is silenced in cells bearing the acute myeloid leukemia-1 eight-twenty-one (AML1/ETO) and promyelocytic leukemia/retinoic acid receptor (PML/RAR) leukemogenic fusion proteins. A role for PIR in myeloid differentiation has not to date been reported. In this study we show that PIR expression is significantly repressed in a large proportion of acute myeloid leukemias (AMLs), regardless of subtype or underlying karyotypic abnormalities. We show that PIR expression increases during in vitro myeloid differentiation of primary hematopoietic precursor cells, and that ablation of PIR in the U937 myelomonocytic cell line or in murine primary hematopoietic precursor cells results in impairment of terminal myeloid differentiation. Gene expression profiling of U937 cells after knockdown of PIR revealed increased expression of genes associated with the early phases of hematopoiesis, in particular, homeobox A (HOXA) genes. Our results suggest that PIR is required for terminal myeloid maturation, and its downregulation may contribute to the differentiation arrest associated with AML.

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Identification of Pirin, a Novel Highly Conserved Nuclear Protein

Cited by 116 publications

References 43 publications

The Bcl-3 oncoprotein acts as a bridging factor between NF-κB/Rel and nuclear co-regulators

The Bcl-3 oncoprotein acts as a bridging factor between NF-κB/Rel and nuclear co-regulators

Pirin Inhibits Cellular Senescence in Melanocytic Cells

Pirin downregulation is a feature of AML and leads to impairment of terminal myeloid differentiation

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