Distinct motifs in the intracellular domain of human CD30 differentially activate canonical and alternative transcription factor NF-κB signaling.

The TNF-receptor superfamily member CD30 is expressed on normal and malignant lymphocytes, including anaplastic large cell lymphoma (ALCL) cells. CD30 transmits multiple effects, including activation of NF-κB signaling, cell proliferation, growth arrest and apoptosis. How CD30 generates these pleiot...

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Autores principales:	Sarah L Buchan, Aymen Al-Shamkhani
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fb6d591d4eea4c12a9364ecbc7a682ca
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spelling	oai:doaj.org-article:fb6d591d4eea4c12a9364ecbc7a682ca2021-11-18T07:05:10ZDistinct motifs in the intracellular domain of human CD30 differentially activate canonical and alternative transcription factor NF-κB signaling.1932-620310.1371/journal.pone.0045244https://doaj.org/article/fb6d591d4eea4c12a9364ecbc7a682ca2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23028875/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The TNF-receptor superfamily member CD30 is expressed on normal and malignant lymphocytes, including anaplastic large cell lymphoma (ALCL) cells. CD30 transmits multiple effects, including activation of NF-κB signaling, cell proliferation, growth arrest and apoptosis. How CD30 generates these pleiotropic effects is currently unknown. Herein we describe ALCL cells expressing truncated forms of the CD30 intracellular domain that allowed us to identify the key regions responsible for transmitting its biological effects in lymphocytes. The first region (CD30(519-537)) activated both the alternative and canonical NF-κB pathways as detected by p100 and IκBα degradation, IKKβ-dependent transcription of both IκBα and the cyclin-dependent kinase inhibitor p21(WAF1/CIP1) and induction of cell cycle arrest. In contrast, the second region of CD30 (CD30(538-595)) induced some aspects of canonical NF-κB activation, including transcription of IκBα, but failed to activate the alternative NF-κB pathway or drive p21(WAF1/CIP1)-mediated cell-cycle arrest. Direct comparison of canonical NF-κB activation by the two motifs revealed 4-fold greater p65 nuclear translocation following CD30(519-537) engagement. These data reveal that independent regions of the CD30 cytoplasmic tail regulate the magnitude and type of NF-κB activation and additionally identify a short motif necessary for CD30-driven growth arrest signals in ALCL cells.Sarah L BuchanAymen Al-ShamkhaniPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 9, p e45244 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sarah L Buchan Aymen Al-Shamkhani Distinct motifs in the intracellular domain of human CD30 differentially activate canonical and alternative transcription factor NF-κB signaling.
description	The TNF-receptor superfamily member CD30 is expressed on normal and malignant lymphocytes, including anaplastic large cell lymphoma (ALCL) cells. CD30 transmits multiple effects, including activation of NF-κB signaling, cell proliferation, growth arrest and apoptosis. How CD30 generates these pleiotropic effects is currently unknown. Herein we describe ALCL cells expressing truncated forms of the CD30 intracellular domain that allowed us to identify the key regions responsible for transmitting its biological effects in lymphocytes. The first region (CD30(519-537)) activated both the alternative and canonical NF-κB pathways as detected by p100 and IκBα degradation, IKKβ-dependent transcription of both IκBα and the cyclin-dependent kinase inhibitor p21(WAF1/CIP1) and induction of cell cycle arrest. In contrast, the second region of CD30 (CD30(538-595)) induced some aspects of canonical NF-κB activation, including transcription of IκBα, but failed to activate the alternative NF-κB pathway or drive p21(WAF1/CIP1)-mediated cell-cycle arrest. Direct comparison of canonical NF-κB activation by the two motifs revealed 4-fold greater p65 nuclear translocation following CD30(519-537) engagement. These data reveal that independent regions of the CD30 cytoplasmic tail regulate the magnitude and type of NF-κB activation and additionally identify a short motif necessary for CD30-driven growth arrest signals in ALCL cells.
format	article
author	Sarah L Buchan Aymen Al-Shamkhani
author_facet	Sarah L Buchan Aymen Al-Shamkhani
author_sort	Sarah L Buchan
title	Distinct motifs in the intracellular domain of human CD30 differentially activate canonical and alternative transcription factor NF-κB signaling.
title_short	Distinct motifs in the intracellular domain of human CD30 differentially activate canonical and alternative transcription factor NF-κB signaling.
title_full	Distinct motifs in the intracellular domain of human CD30 differentially activate canonical and alternative transcription factor NF-κB signaling.
title_fullStr	Distinct motifs in the intracellular domain of human CD30 differentially activate canonical and alternative transcription factor NF-κB signaling.
title_full_unstemmed	Distinct motifs in the intracellular domain of human CD30 differentially activate canonical and alternative transcription factor NF-κB signaling.
title_sort	distinct motifs in the intracellular domain of human cd30 differentially activate canonical and alternative transcription factor nf-κb signaling.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/fb6d591d4eea4c12a9364ecbc7a682ca
work_keys_str_mv	AT sarahlbuchan distinctmotifsintheintracellulardomainofhumancd30differentiallyactivatecanonicalandalternativetranscriptionfactornfkbsignaling AT aymenalshamkhani distinctmotifsintheintracellulardomainofhumancd30differentiallyactivatecanonicalandalternativetranscriptionfactornfkbsignaling
_version_	1718424016157409280

Distinct motifs in the intracellular domain of human CD30 differentially activate canonical and alternative transcription factor NF-κB signaling.

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