{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2022,4,3]],"date-time":"2022-04-03T18:20:38Z","timestamp":1649010038147},"reference-count":38,"publisher":"Portland Press Ltd.","issue":"5","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,3,1]]},"abstract":"<jats:p>Prrxl1 encodes for a paired-like homeodomain transcription factor essential for the correct establishment of the dorsal root ganglion \u2014 spinal cord nociceptive circuitry during development. Prrxl1-null mice display gross anatomical disruption of this circuitry, which translates to a markedly diminished sensitivity to noxious stimuli. Here, by the use of an immunoprecipitation and mass spectrometry approach, we identify five highly conserved phosphorylation sites (T110, S119, S231, S233 and S251) in PRRXL1 primary structure. Four are phospho-S\/T-P sites, which suggest a role for the prolyl isomerase PIN1 in regulating PRRXL1. Accordingly, PRRXL1 physically interacts with PIN1 and displays diminished transcriptional activity in a Pin1-null cell line. Additionally, these S\/T-P sites seem to be important for PRRXL1 conformation, and their point mutation to alanine or aspartate down-regulates PRRXL1 transcriptional activity. Altogether, our findings provide evidence for a putative novel role of PIN1 in the development of the nociceptive system and indicate phosphorylation-mediated conformational changes as a mechanism for regulating the PRRXL1 role in the process.<\/jats:p>","DOI":"10.1042\/bcj20160560","type":"journal-article","created":{"date-parts":[[2017,1,4]],"date-time":"2017-01-04T01:50:20Z","timestamp":1483494620000},"page":"683-697","update-policy":"http:\/\/dx.doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A role for prolyl isomerase PIN1 in the phosphorylation-dependent modulation of PRRXL1 function"],"prefix":"10.1042","volume":"474","author":[{"given":"Ricardo","family":"Soares-dos-Reis","sequence":"first","affiliation":[{"name":"Departamento de Biomedicina, Unidade de Biologia Experimental, Faculdade de Medicina da Universidade do Porto, Porto, Portugal"},{"name":"i3S \u2014 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Porto, Portugal"},{"name":"IBMC \u2014 Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal"},{"name":"Departamento de Neuroci\u00eancias Cl\u00ednicas e Sa\u00fade Mental, Faculdade de Medicina da Universidade do Porto, Porto, Portugal"},{"name":"Servi\u00e7o de Neurologia, Centro Hospitalar de S\u00e3o Jo\u00e3o, Porto, Portugal"}]},{"given":"Ana Sofia","family":"Pessoa","sequence":"additional","affiliation":[{"name":"Departamento de Biomedicina, Unidade de Biologia Experimental, Faculdade de Medicina da Universidade do Porto, Porto, Portugal"},{"name":"IBMC \u2014 Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal"},{"name":"Servi\u00e7o de Medicina, Centro Hospitalar do M\u00e9dio Ave, Vila Nova de Famalic\u00e3o, Portugal"}]},{"given":"Ana Filipa","family":"Dias","sequence":"additional","affiliation":[{"name":"Departamento de Biomedicina, Unidade de Biologia Experimental, Faculdade de Medicina da Universidade do Porto, Porto, Portugal"},{"name":"i3S \u2014 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Porto, Portugal"},{"name":"IBMC \u2014 Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal"}]},{"given":"Miguel","family":"Falc\u00e3o","sequence":"additional","affiliation":[{"name":"Departamento de Biomedicina, Unidade de Biologia Experimental, Faculdade de Medicina da Universidade do Porto, Porto, Portugal"},{"name":"i3S \u2014 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Porto, Portugal"},{"name":"IBMC \u2014 Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal"}]},{"given":"Mariana Raimundo","family":"Matos","sequence":"additional","affiliation":[{"name":"Departamento de Biomedicina, Unidade de Biologia Experimental, Faculdade de Medicina da Universidade do Porto, Porto, Portugal"},{"name":"i3S \u2014 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Porto, Portugal"},{"name":"IBMC \u2014 Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal"}]},{"given":"Rui","family":"Vitorino","sequence":"additional","affiliation":[{"name":"Departamento de Cirurgia e Fisiologia, Faculdade de Medicina da Universidade do Porto, Porto, Portugal"},{"name":"Departamento de Ci\u00eancias M\u00e9dicas, iBiMED \u2014 Instituto de Biomedicina da Universidade de Aveiro, Aveiro, Portugal"}]},{"given":"Filipe Almeida","family":"Monteiro","sequence":"additional","affiliation":[{"name":"Departamento de Biomedicina, Unidade de Biologia Experimental, Faculdade de Medicina da Universidade do Porto, Porto, Portugal"},{"name":"i3S \u2014 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Porto, Portugal"},{"name":"IBMC \u2014 Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal"}]},{"given":"Deolinda","family":"Lima","sequence":"additional","affiliation":[{"name":"Departamento de Biomedicina, Unidade de Biologia Experimental, Faculdade de Medicina da Universidade do Porto, Porto, Portugal"},{"name":"i3S \u2014 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Porto, Portugal"},{"name":"IBMC \u2014 Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal"}]},{"given":"Carlos","family":"Reguenga","sequence":"additional","affiliation":[{"name":"Departamento de Biomedicina, Unidade de Biologia Experimental, Faculdade de Medicina da Universidade do Porto, Porto, Portugal"},{"name":"i3S \u2014 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Porto, Portugal"},{"name":"IBMC \u2014 Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal"}]}],"member":"288","published-online":{"date-parts":[[2017,2,20]]},"reference":[{"key":"2021112216502913900_BCJ-2016-0560C1","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1016\/j.conb.2006.06.002","article-title":"The development and modulation of nociceptive circuitry","volume":"16","author":"Zhang","year":"2006","journal-title":"Curr. Opin. Neurobiol."},{"key":"2021112216502913900_BCJ-2016-0560C2","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1038\/nn1221","article-title":"Tlx3 and Tlx1 are post-mitotic selector genes determining glutamatergic over GABAergic cell fates","volume":"7","author":"Cheng","year":"2004","journal-title":"Nat. Neurosci."},{"key":"2021112216502913900_BCJ-2016-0560C3","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1016\/j.mcn.2006.07.013","article-title":"Involvement of DRG11 in the development of the primary afferent nociceptive system","volume":"33","author":"Rebelo","year":"2006","journal-title":"Mol. Cell. Neurosci."},{"key":"2021112216502913900_BCJ-2016-0560C4","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/S0896-6273(01)00341-5","article-title":"The paired homeodomain protein DRG11 is required for the projection of cutaneous sensory afferent fibers to the dorsal spinal cord","volume":"31","author":"Chen","year":"2001","journal-title":"Neuron"},{"key":"2021112216502913900_BCJ-2016-0560C5","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1016\/j.ejpain.2010.10.007","article-title":"Postnatal expression of the homeobox gene Prrxl1 (Drg11) is increased in inflammatory but not neuropathic pain","volume":"15","author":"Monteiro","year":"2011","journal-title":"Eur. J. Pain"},{"key":"2021112216502913900_BCJ-2016-0560C6","doi-asserted-by":"publisher","first-page":"2513","DOI":"10.1098\/rstb.2012.0013","article-title":"Why nature chose phosphate to modify proteins","volume":"367","author":"Hunter","year":"2012","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"2021112216502913900_BCJ-2016-0560C7","doi-asserted-by":"publisher","first-page":"1720","DOI":"10.1128\/MCB.06440-11","article-title":"Transcriptional activity of neural retina leucine zipper (Nrl) is regulated by c-Jun N-terminal kinase and Tip60 during retina development","volume":"32","author":"Kim","year":"2012","journal-title":"Mol. Cell. Biol."},{"key":"2021112216502913900_BCJ-2016-0560C8","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1016\/j.neuron.2011.01.030","article-title":"Phosphorylation regulates OLIG2 cofactor choice and the motor neuron-oligodendrocyte fate switch","volume":"69","author":"Li","year":"2011","journal-title":"Neuron"},{"key":"2021112216502913900_BCJ-2016-0560C9","doi-asserted-by":"publisher","first-page":"3288","DOI":"10.1093\/nar\/gkp197","article-title":"CK2 phosphorylation of the PRH\/Hex homeodomain functions as a reversible switch for DNA binding","volume":"37","author":"Soufi","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"2021112216502913900_BCJ-2016-0560C10","doi-asserted-by":"publisher","first-page":"3795","DOI":"10.1021\/bi970982t","article-title":"Phosphorylation of the cAMP response element binding protein CREB by cAMP-dependent protein kinase A and glycogen synthase kinase-3 alters DNA-binding affinity, conformation, and increases net charge","volume":"37","author":"Bullock","year":"1998","journal-title":"Biochemistry"},{"key":"2021112216502913900_BCJ-2016-0560C11","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1016\/j.bbagrm.2014.08.007","article-title":"Dual role of Tlx3 as modulator of Prrxl1 transcription and phosphorylation","volume":"1839","author":"Regadas","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"2021112216502913900_BCJ-2016-0560C12","doi-asserted-by":"publisher","first-page":"2653","DOI":"10.1002\/dvdy.21271","article-title":"DRG11 immunohistochemical expression during embryonic development in the mouse","volume":"236","author":"Rebelo","year":"2007","journal-title":"Dev. Dyn."},{"key":"2021112216502913900_BCJ-2016-0560C13","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1042\/BJ20131014","article-title":"Ser119 phosphorylation modulates the activity and conformation of PRRXL1, a homeodomain transcription factor","volume":"459","author":"Soares-dos-Reis","year":"2014","journal-title":"Biochem. J."},{"key":"2021112216502913900_BCJ-2016-0560C14","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1016\/S0960-9822(95)00151-5","article-title":"Transcriptional control by protein phosphorylation: signal transmission from the cell surface to the nucleus","volume":"5","author":"Karin","year":"1995","journal-title":"Curr. Biol."},{"key":"2021112216502913900_BCJ-2016-0560C15","doi-asserted-by":"crossref","first-page":"RE8","DOI":"10.1126\/stke.2003.179.re8","article-title":"The structure and function of proline recognition domains","volume":"2003","author":"Zarrinpar","year":"2003","journal-title":"Sci. STKE"},{"key":"2021112216502913900_BCJ-2016-0560C16","doi-asserted-by":"publisher","first-page":"1957","DOI":"10.1126\/science.278.5345.1957","article-title":"Sequence-specific and phosphorylation-dependent proline isomerization: a potential mitotic regulatory mechanism","volume":"278","author":"Yaffe","year":"1997","journal-title":"Science"},{"key":"2021112216502913900_BCJ-2016-0560C17","doi-asserted-by":"publisher","first-page":"904","DOI":"10.1038\/nrm2261","article-title":"The prolyl isomerase PIN1: a pivotal new twist in phosphorylation signalling and disease","volume":"8","author":"Lu","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2021112216502913900_BCJ-2016-0560C18","doi-asserted-by":"publisher","first-page":"1332","DOI":"10.4161\/cc.6.11.4316","article-title":"Pin1 in neuronal apoptosis","volume":"6","author":"Becker","year":"2007","journal-title":"Cell Cycle"},{"key":"2021112216502913900_BCJ-2016-0560C19","doi-asserted-by":"publisher","first-page":"2966","DOI":"10.1128\/MCB.05688-11","article-title":"Prolyl isomerase Pin1 regulates neuronal differentiation via \u03b2-catenin","volume":"32","author":"Nakamura","year":"2012","journal-title":"Mol. Cell. Biol."},{"key":"2021112216502913900_BCJ-2016-0560C20","doi-asserted-by":"publisher","first-page":"E3929","DOI":"10.1073\/pnas.1414770111","article-title":"C-terminal domain small phosphatase 1 and MAP kinase reciprocally control REST stability and neuronal differentiation","volume":"111","author":"Nesti","year":"2014","journal-title":"Proc. Natl Acad. Sci. U.S.A."},{"key":"2021112216502913900_BCJ-2016-0560C21","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1016\/j.celrep.2015.09.026","article-title":"Prolyl isomerase Pin1 regulates axon guidance by stabilizing CRMP2A selectively in distal axons","volume":"13","author":"Balastik","year":"2015","journal-title":"Cell Rep."},{"key":"2021112216502913900_BCJ-2016-0560C22","doi-asserted-by":"publisher","first-page":"2027","DOI":"10.1523\/JNEUROSCI.4115-03.2004","article-title":"DRAGON: a member of the repulsive guidance molecule-related family of neuronal- and muscle-expressed membrane proteins is regulated by DRG11 and has neuronal adhesive properties","volume":"24","author":"Samad","year":"2004","journal-title":"J. Neurosci."},{"key":"2021112216502913900_BCJ-2016-0560C23","doi-asserted-by":"publisher","first-page":"36285","DOI":"10.1074\/jbc.M113.491993","article-title":"Several cis-regulatory elements control mRNA stability, translation efficiency, and expression pattern of Prrxl1 (paired related homeobox protein-like 1)","volume":"288","author":"Regadas","year":"2013","journal-title":"J. Biol. Chem."},{"key":"2021112216502913900_BCJ-2016-0560C24","doi-asserted-by":"publisher","first-page":"7597","DOI":"10.1158\/0008-5472.CAN-08-1059","article-title":"The peptidyl-isomerase Pin1 regulates p27kip1 expression through inhibition of Forkhead box O tumor suppressors","volume":"68","author":"Brenkman","year":"2008","journal-title":"Cancer Res."},{"key":"2021112216502913900_BCJ-2016-0560C25","doi-asserted-by":"publisher","first-page":"1449","DOI":"10.1111\/ejn.13214","article-title":"Zinc finger transcription factor Casz1 expression is regulated by homeodomain transcription factor Prrxl1 in embryonic spinal dorsal horn late-born excitatory interneurons","volume":"43","author":"Monteiro","year":"2016","journal-title":"Eur. J. Neurosci."},{"key":"2021112216502913900_BCJ-2016-0560C26","doi-asserted-by":"publisher","first-page":"3475","DOI":"10.1016\/j.febslet.2014.08.006","article-title":"Paired related homeobox protein-like 1 (Prrxl1) controls its own expression by a transcriptional autorepression mechanism","volume":"588","author":"Monteiro","year":"2014","journal-title":"FEBS Lett."},{"key":"2021112216502913900_BCJ-2016-0560C27","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1016\/j.tibs.2011.07.001","article-title":"Prolyl isomerase Pin1 as a molecular switch to determine the fate of phosphoproteins","volume":"36","author":"Liou","year":"2011","journal-title":"Trends Biochem. Sci."},{"key":"2021112216502913900_BCJ-2016-0560C28","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1016\/j.ydbio.2006.01.033","article-title":"Molecular mapping of developing dorsal horn-enriched genes by microarray and dorsal\/ventral subtractive screening","volume":"292","author":"Li","year":"2006","journal-title":"Dev. Biol."},{"key":"2021112216502913900_BCJ-2016-0560C29","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/j.tcb.2009.02.003","article-title":"A post-translational modification code for transcription factors: sorting through a sea of signals","volume":"19","author":"Benayoun","year":"2009","journal-title":"Trends Cell Biol."},{"key":"2021112216502913900_BCJ-2016-0560C30","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/1745-6150-5-6","article-title":"Cooperativity within proximal phosphorylation sites is revealed from large-scale proteomics data","volume":"5","author":"Schweiger","year":"2010","journal-title":"Biol. Direct"},{"key":"2021112216502913900_BCJ-2016-0560C31","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1038\/ncb0505-435","article-title":"Phosphorylation-specific prolyl isomerization: is there an underlying theme?","volume":"7","author":"Wulf","year":"2005","journal-title":"Nat. Cell Biol."},{"key":"2021112216502913900_BCJ-2016-0560C32","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1093\/embo-reports\/kvf118","article-title":"Peptidyl-prolyl isomerases: a new twist to transcription","volume":"3","author":"Shaw","year":"2002","journal-title":"EMBO Rep."},{"key":"2021112216502913900_BCJ-2016-0560C33","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1038\/cdd.2013.160","article-title":"Prolyl isomerase Pin1 and protein kinase HIPK2 cooperate to promote cortical neurogenesis by suppressing Groucho\/TLE:Hes1-mediated inhibition of neuronal differentiation","volume":"21","author":"Ciarapica","year":"2014","journal-title":"Cell Death Differ."},{"key":"2021112216502913900_BCJ-2016-0560C34","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1128\/MCB.00904-12","article-title":"An unusual two-step control of CPEB destruction by Pin1","volume":"33","author":"Nechama","year":"2013","journal-title":"Mol. Cell. Biol."},{"key":"2021112216502913900_BCJ-2016-0560C35","doi-asserted-by":"publisher","first-page":"12125","DOI":"10.1021\/bi0608820","article-title":"Thermodynamics of phosphopeptide binding to the human peptidyl prolyl cis\/trans isomerase Pin1","volume":"45","author":"Daum","year":"2006","journal-title":"Biochemistry"},{"key":"2021112216502913900_BCJ-2016-0560C36","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1016\/S0092-8674(00)80273-1","article-title":"Structural and functional analysis of the mitotic rotamase Pin1 suggests substrate recognition is phosphorylation dependent","volume":"89","author":"Ranganathan","year":"1997","journal-title":"Cell"},{"key":"2021112216502913900_BCJ-2016-0560C37","doi-asserted-by":"publisher","first-page":"9706","DOI":"10.1523\/JNEUROSCI.1109-12.2012","article-title":"Tlx3 and Runx1 act in combination to coordinate the development of a cohort of nociceptors, thermoceptors, and pruriceptors","volume":"32","author":"Lopes","year":"2012","journal-title":"J. Neurosci."},{"key":"2021112216502913900_BCJ-2016-0560C38","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1002\/jcp.24462","article-title":"Pin1-mediated prolyl isomerization of Runx1 affects PU.1 expression in pre-monocytes","volume":"229","author":"Islam","year":"2014","journal-title":"J. Cell. Physiol."}],"container-title":["Biochemical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/474\/5\/683\/690523\/bcj-2016-0560.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/474\/5\/683\/690523\/bcj-2016-0560.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,22]],"date-time":"2021-11-22T23:35:03Z","timestamp":1637624103000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemj\/article\/474\/5\/683\/49703\/A-role-for-prolyl-isomerase-PIN1-in-the"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,2,20]]},"references-count":38,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2017,3,1]]}},"URL":"https:\/\/doi.org\/10.1042\/bcj20160560","relation":{},"ISSN":["0264-6021","1470-8728"],"issn-type":[{"value":"0264-6021","type":"print"},{"value":"1470-8728","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,2,20]]}}}