Myb-binding protein 1a is a nucleocytoplasmic shuttling protein that utilizes CRM1-dependent and independent nuclear export pathways

Keough, Rebecca A.; Macmillan, Elizabeth M.; Lutwyche, Jodi K.; Gardner, Jennifer M.; Tavner, Fiona; Jans, David A.; Henderson, Beric R.; Gonda, Thomas J.

doi:10.1016/s0014-4827(03)00262-3

Cited by 23 publications

(23 citation statements)

References 35 publications

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“…These antibodies preferentially stained few nuclear organelles, possibly nucleoli, in exponentially growing NIH 3T3 cells (Fig. 5A), as expected (26,47). The nucleolar nature of the p160-positive nuclear bodies was confirmed by costaining them with antibodies to nucleolin, a specific marker of nucleoli (not shown).…”

Section: Vol 27 2007 P160 Myb-binding Protein Is a Competitor Of Prsupporting

confidence: 62%

“…In vitro, p160 (and p67) competes with Pbx1 for Prep1 binding and ectopic p160 expression inhibits the binding of Prep1/Pbx1 to the enhancer of HoxB2 and the retinoic acid (RA) induction of HoxB2 transcription. In the cell, p160 and Prep1 are found in the nucleolus (26) and nucleus (4), respectively. Interestingly, treatment of cells with actinomycin D (ActD), which extrudes p160 from the nucleolus, induces colocalization and coimmunoprecipitation of the endogenous proteins.…”

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confidence: 99%

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p160 Myb-Binding Protein Interacts with Prep1 and Inhibits Its Transcriptional Activity

Dı́az

Mori

Longobardi

et al. 2007

Molecular and Cellular Biology

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Prep1 is known to interact in vivo with Pbx1 to regulate development and organogenesis. We have identified a novel Prep1-interacting protein, p160 c-Myb binding protein (p160). p160 and Pbx1 compete for Prep1 in vitro, and p160 inhibits Prep1-dependent HoxB2 expression in retinoic acid-treated NT2-D1 cells. The Nterminal physiologically truncated form of p160, p67, binds the sequence 63LFPLL67 in the HR1 domain of Prep1. Mutation of both L63 and L66 impairs the binding of Prep1 to both p160/p67 and Pbx1. The sequences required to bind Prep1 are mainly located in residues 51 to 151. Immunofluorescence colocalization and coimmunoprecipitation of endogenous p160 and Prep1 are induced by ActD, which translocates p160 from the nucleolus to the nucleoplasm. These data therefore show that p160 is a novel regulator of Prep1-Pbx1 transcriptional activity.

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Section: Vol 27 2007 P160 Myb-binding Protein Is a Competitor Of Prsupporting

confidence: 62%

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confidence: 99%

p160 Myb-Binding Protein Interacts with Prep1 and Inhibits Its Transcriptional Activity

Dı́az

Mori

Longobardi

et al. 2007

Molecular and Cellular Biology

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“…The majority of the phosphorylation sites mapped in MYBBP1A in these studies (18 of a total of 21) reside within the ϳ200-amino acid-long C-terminal portion of the protein, which has been shown to be relevant for its nuclear and nucleolar localization (73). Notably, MYBBP1A was also found to be a component of the proteome as well as the phospho-proteome of the human mitotic spindle (71,74), pointing to an additional co-localization where Aurora B kinase may encounter and phosphorylate MYBBP1A.…”

Section: Discussionmentioning

confidence: 86%

Identification of Myb-binding Protein 1A (MYBBP1A) as a Novel Substrate for Aurora B Kinase

Perrera

Colombo

Valsasina

et al. 2010

Journal of Biological Chemistry

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Aurora kinases are mitotic enzymes involved in centrosome maturation and separation, spindle assembly and stability, and chromosome condensation, segregation, and cytokinesis and represent well known targets for cancer therapy because their deregulation has been linked to tumorigenesis. The availability of suitable markers is of crucial importance to investigate the functions of Auroras and monitor kinase inhibition in in vivo models and in clinical trials. Extending the knowledge on Aurora substrates could help to better understand their biology and could be a source for clinical biomarkers. Using biochemical, mass spectrometric, and cellular approaches, we identified MYBBP1A as a novel Aurora B substrate and serine 1303 as the major phosphorylation site. MYBBP1A is phosphorylated in nocodazole-arrested cells and is dephosphorylated upon Aurora B silencing or by treatment with Danusertib, a small molecule inhibitor of Aurora kinases. Furthermore, we show that MYBBP1A depletion by RNA interference causes mitotic progression delay and spindle assembly defects. MYBBP1A has until now been described as a nucleolar protein, mainly involved in transcriptional regulation. The results presented herein show MYBBP1A as a novel Aurora B kinase substrate and reveal a not yet recognized link of this nucleolar protein to mitosis.

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“…Recently, numerous proteins (cdc14, NPM, cyclin E, Mybbp1a, telomerase reverse transcriptase, and others) have been shown to continuously shuttle from the nucleolus to various subcellular compartments in a regulated manner, providing evidence that the nucleolus is a dynamic site of multiple cellular events (4,7,21,22,52).…”

Section: Discussionmentioning

confidence: 99%

Nucleophosmin Is Essential for Ribosomal Protein L5 Nuclear Export

Maggi

Brady

et al. 2006

Molecular and Cellular Biology

196

194

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Nucleophosmin (NPM/B23) is a key regulator in the regulation of a number of processes including centrosome duplication, maintenance of genomic integrity, and ribosome biogenesis. While the mechanisms underlying NPM function are largely uncharacterized, NPM loss results in severe dysregulation of developmental and growth-related events. We show that NPM utilizes a conserved CRM1-dependent nuclear export sequence in its amino terminus to enable its shuttling between the nucleolus/nucleus and cytoplasm. In search of NPM trafficking targets, we biochemically purified NPM-bound protein complexes from HeLa cell lysates. Consistent with NPM's proposed role in ribosome biogenesis, we isolated ribosomal protein L5 (rpL5), a known chaperone for the 5S rRNA. Direct interaction of NPM with rpL5 mediated the colocalization of NPM with maturing nuclear 60S ribosomal subunits, as well as newly exported and assembled 80S ribosomes and polysomes. Inhibition of NPM shuttling or loss of NPM blocked the nuclear export of rpL5 and 5S rRNA, resulting in cell cycle arrest and demonstrating that NPM and its nuclear export provide a unique and necessary chaperoning activity to rpL5/5S.As the most prominent of subnuclear structures, the nucleolus has long been recognized as the site of active transcription of rRNA and ribosome assembly (8). Various nucleolar proteins, RNAs, and other factors have been implicated in the complex process of ribosome production and maturation (18). Recently, several groups reported the successful isolation and mapping of the mammalian nucleolar proteome (1, 2, 44). While these studies clearly identified proteins and ribonucleoproteins with purported roles in ribosome biogenesis, a surprising number of proteins within the nucleolar proteome (Ͼ100) have no known function. In previous decades, it was assumed that all nucleolar proteins must somehow contribute to static ribosome biogenesis simply by virtue of their localization. However, more-recent findings have demonstrated that the nucleolus is a dynamic subnuclear organelle which regulates numerous cellular processes, prompting a broadened view of the potential functions of nucleolar proteins (28).Nucleophosmin (NPM/B23) is an abundant phosphoprotein that resides within the granular regions of the nucleolus (46). Proliferating cells express NPM at high levels (9, 13), and NPM has been associated with a variety of cellular events, including ribosomal biogenesis, protein chaperoning, and centrosome duplication (13,23,35,36). Structurally, NPM is present in both monomeric and multimeric states, although NPM multimers appear predominant in the nucleolus and may be crucial for the assembly of maturing ribosomes (33,34,53). Furthermore, NPM, along with other nucleolar proteins, is believed (or has been shown) to actively mobilize into distinct subcellular pools, supporting the notion that NPM trafficking may be essential for its (proper) function (6). Indeed, NPM's transit from the nucleolus/nucleus is an essential event in S phase progression; when NPM export was...

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Myb-binding protein 1a is a nucleocytoplasmic shuttling protein that utilizes CRM1-dependent and independent nuclear export pathways

Cited by 23 publications

References 35 publications

p160 Myb-Binding Protein Interacts with Prep1 and Inhibits Its Transcriptional Activity

p160 Myb-Binding Protein Interacts with Prep1 and Inhibits Its Transcriptional Activity

Identification of Myb-binding Protein 1A (MYBBP1A) as a Novel Substrate for Aurora B Kinase

Nucleophosmin Is Essential for Ribosomal Protein L5 Nuclear Export

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