Functional interaction of Yaf2 with the central region of MycN

Bannasch, Detlev; Mädge, Britta; Schwab, Manfred

doi:10.1038/sj.onc.1204747

Cited by 17 publications

(11 citation statements)

References 21 publications

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“…YAF2 has promyogenic regulatory role, since YAF2 overexpression stimulates myogenic promoter activity in C2 myoblasts [246]. It was also found that Yaf2 enhances MycN dependent transcriptional activation in human neuroblastoma cell lines [247], however inhibits MYC mediated transactivation and transformation [248] suggesting its potential role in tumorigenic processes. Importantly, YAF2 serves as a mediator to bridge between YY1 and PRC complex proteins, such as EZH2 or RING1/RNF2 [251] and this interaction is essential for PRC recruitment in mammals [252].…”

Section: Core Members Of Ncprcsmentioning

confidence: 87%

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From Flies to Mice: The Emerging Role of Non-Canonical PRC1 Members in Mammalian Development

2018

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Originally two types of Polycomb Repressive Complexes (PRCs) were described, canonical PRC1 (cPRC1) and PRC2. Recently, a versatile set of complexes were identified and brought up several dilemmas in PRC mediated repression. These new class of complexes were named as non-canonical PRC1s (ncPRC1s). Both cPRC1s and ncPRC1s contain Ring finger protein (RING1, RNF2) and Polycomb group ring finger catalytic (PCGF) core, but in ncPRCs, RING and YY1 binding protein (RYBP), or YY1 associated factor 2 (YAF2), replaces the Chromobox (CBX) and Polyhomeotic (PHC) subunits found in cPRC1s. Additionally, ncPRC1 subunits can associate with versatile accessory proteins, which determine their functional specificity. Homozygous null mutations of the ncPRC members in mice are often lethal or cause infertility, which underlines their essential functions in mammalian development. In this review, we summarize the mouse knockout phenotypes of subunits of the six major ncPRCs. We highlight several aspects of their discovery from fly to mice and emerging role in target recognition, embryogenesis and cell-fate decision making. We gathered data from stem cell mediated in vitro differentiation assays and genetically engineered mouse models. Accumulating evidence suggests that ncPRC1s play profound role in mammalian embryogenesis by regulating gene expression during lineage specification of pluripotent stem cells.

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Section: Core Members Of Ncprcsmentioning

confidence: 87%

“…The human YAF2 was isolated as an interacting partner for YY1 [246]. Later, it was found that YAF2 also interacts with MYCN [247], MYC [248] and RING1/RNF2 [249]. YAF2 is paralog of RYBP [239] and together they constitute a functionally different cofactor family for YY1 and E4TF1/hGABP transcription factors [250].…”

Section: Core Members Of Ncprcsmentioning

confidence: 99%

From Flies to Mice: The Emerging Role of Non-Canonical PRC1 Members in Mammalian Development

2018

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“…With the identification of two additional proteins, Mad and Mxi1, that both bind to Max,65,66 the matter has become more complex, and it is clear that Myc proteins are members of a nucleoprotein complex. Even more, the central region of MYCN appears to be a target for interacting proteins as well, as recently demonstrated by the binding of YAF2 67…”

Section: Regulation Of Mycn Protein By Interacting Proteinsmentioning

confidence: 88%

Amplified MYCN in Human Neuroblastoma

Schwab

2002

Annals of the New York Academy of Sciences

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Increase in the dosage of cellular oncogenes by DNA amplification is a frequent genetic alteration of cancer cells. In neuroblastoma, amplification of the gene MYCN has been associated with aggressively growing cancers and is an indicator for poor prognosis. MYCN amplification is of predictive value in identifying patients with neuroblastoma who require specific therapeutic regimens and those who do not benefit from chemotherapy.

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“…This protein was initially described as an interacting ligand for the YY1 protein [Kalenik et al, 1997], but subsequent work has identified additional transcription factors that bind Yaf2. The activities of the DNA-binding MYC proteins were modified by Yaf2 [Bannasch et al, 2001; Madge et al, 2003]. MycN transactivation was enhanced, but that of c-MYC was inhibited suggesting Yaf2 is multifunctional.…”

Section: Discussionmentioning

confidence: 99%

PcG recruitment by the YY1 REPO domain can be mediated by Yaf2

Wilkinson

Pratt

Atchison

2009

J of Cellular Biochemistry

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The Polycomb Group (PcG) complex of transcriptional repressors is critical for the maintenance of stage-specific developmental gene expression, stem cell maintenance and for large-scale chromosomal dynamics. Functional deficiency of a single PcG gene can severely compromise PcG function, leading to developmental defects, embryonic lethality, or a number of malignancies. Despite the critical nature of PcG proteins, the mechanisms by which these complexes mediate their effects are relatively uncharacterized. Nearly all vertebrate PcG proteins lack inherent DNA binding capacity, making it unclear how they are targeted to Polycomb response element (PRE) sequences. Transcription factor YY1 is a functional ortholog of a Drosophila PcG protein, Pleiohomeotic (PHO), one of the few PcG proteins with specific DNA binding capability, and YY1 can recruit PcG proteins to specific DNA sequences. A small 25 amino acid YY1 domain (the REPO domain) is necessary and sufficient for recruitment of PcG proteins to DNA and for transcriptional repression. We show here that the YY1 REPO domain interacts with PcG protein Yaf2 and recruits Yaf2 to DNA. Interaction is lost when the YY1 REPO domain is deleted. In addition we show that Yaf2, when linked to a heterologous DNA binding domain, can recruit PcG proteins to DNA leading to transcriptional repression. When the Drosophila homolog of Yaf2 (dRYBP) is mutated, PcG recruitment to DNA is reduced. Taken together, our results suggest that Yaf2 serves as a molecular bridge between YY1 and other PcG complex proteins.

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Functional interaction of Yaf2 with the central region of MycN

Cited by 17 publications

References 21 publications

From Flies to Mice: The Emerging Role of Non-Canonical PRC1 Members in Mammalian Development

From Flies to Mice: The Emerging Role of Non-Canonical PRC1 Members in Mammalian Development

Amplified MYCN in Human Neuroblastoma

PcG recruitment by the YY1 REPO domain can be mediated by Yaf2

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