PB1 Domain Interaction of p62/Seq uestosome 1 and MEKK3 Regulates NF-κB Activation.
Saved in:
| Title: | PB1 Domain Interaction of p62/Seq uestosome 1 and MEKK3 Regulates NF-κB Activation. |
|---|---|
| Authors: | Nakamura, Kazuhiro1, Kimple, Adam J.1, Siderovski, David P.1, Johnson, Gary L.1 garyjohnson@med.unc.edu |
| Source: | Journal of Biological Chemistry. 1/15/2010, Vol. 285 Issue 3, p2077-2089. 13p. |
| Subjects: | Scaffold proteins, Protein kinase C, RNA, Osteitis deformans, Luciferases, Ligands (Biochemistry) |
| Abstract: | p62/Sequestosome 1 is a scaffold protein involved in the regulation of autophagy, trafficking of proteins to the proteasome, and activation of NF-κB. p62 encodes an N-terminal PB1 domain in addition to the ZZ domain, TRAF6-binding domain, LC3 interaction region, and ubiquitin-associated domain;each critical for the physiological function of p62. PB1 domains have a a-grasp topology where the front end of one PB1 domain binds the back end of a second PB1 domain. The p62 PB1 domain homodimerizes as well as heterodimerizes with other PB1 domains. The front end of the PB1 domain in p62 binds the PB1 domain of atypical protein kinases C, the MAPK kinase, MEK5, and the NBR1 protein. Other than its role in homodimerization, the rear end acidic cluster region of the p62 PB1 domain had no previous defined binding partners. Herein, we demonstrate that the rear end acidic cluster region of the p62 PB1 domain binds the front end basic region of the MAPK kinase kinase, MEKK3. p62 and MEKK3 co-localize in speckles or aggregates that are centers for organizing TRAF6-regulated NF-KB signaling and the assembly of polyubiquinated proteins sorting to sequestosomes and proteasomes. The p62-MEKK3 complex binds TRAF6, which regulates the ubiquitination of the IKK complex and NF-κB activation. p62 is required for the association of MEKK3 with TRAF6 and short hairpin RNA knockdown of p62 inhibits IL-1 and MEKK3 activation of NF-κB. The rear end acidic cluster of the p62 PB1 domain is used to organize cytosolic aggregates or speckles-associated TRAF6-p62-MEKK3 complex for control of NF-κB activation. [ABSTRACT FROM AUTHOR] |
| Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Engineering Source |
| FullText | Text: Availability: 0 |
|---|---|
| Header | DbId: egs DbLabel: Engineering Source An: 48778360 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
| IllustrationInfo | |
| Items | – Name: Title Label: Title Group: Ti Data: PB1 Domain Interaction of p62/Seq uestosome 1 and MEKK3 Regulates NF-κB Activation. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Nakamura%2C+Kazuhiro%22">Nakamura, Kazuhiro</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Kimple%2C+Adam+J%2E%22">Kimple, Adam J.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Siderovski%2C+David+P%2E%22">Siderovski, David P.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Johnson%2C+Gary+L%2E%22">Johnson, Gary L.</searchLink><relatesTo>1</relatesTo><i> garyjohnson@med.unc.edu</i> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Journal+of+Biological+Chemistry%22">Journal of Biological Chemistry</searchLink>. 1/15/2010, Vol. 285 Issue 3, p2077-2089. 13p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Scaffold+proteins%22">Scaffold proteins</searchLink><br /><searchLink fieldCode="DE" term="%22Protein+kinase+C%22">Protein kinase C</searchLink><br /><searchLink fieldCode="DE" term="%22RNA%22">RNA</searchLink><br /><searchLink fieldCode="DE" term="%22Osteitis+deformans%22">Osteitis deformans</searchLink><br /><searchLink fieldCode="DE" term="%22Luciferases%22">Luciferases</searchLink><br /><searchLink fieldCode="DE" term="%22Ligands+%28Biochemistry%29%22">Ligands (Biochemistry)</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: p62/Sequestosome 1 is a scaffold protein involved in the regulation of autophagy, trafficking of proteins to the proteasome, and activation of NF-κB. p62 encodes an N-terminal PB1 domain in addition to the ZZ domain, TRAF6-binding domain, LC3 interaction region, and ubiquitin-associated domain;each critical for the physiological function of p62. PB1 domains have a a-grasp topology where the front end of one PB1 domain binds the back end of a second PB1 domain. The p62 PB1 domain homodimerizes as well as heterodimerizes with other PB1 domains. The front end of the PB1 domain in p62 binds the PB1 domain of atypical protein kinases C, the MAPK kinase, MEK5, and the NBR1 protein. Other than its role in homodimerization, the rear end acidic cluster region of the p62 PB1 domain had no previous defined binding partners. Herein, we demonstrate that the rear end acidic cluster region of the p62 PB1 domain binds the front end basic region of the MAPK kinase kinase, MEKK3. p62 and MEKK3 co-localize in speckles or aggregates that are centers for organizing TRAF6-regulated NF-KB signaling and the assembly of polyubiquinated proteins sorting to sequestosomes and proteasomes. The p62-MEKK3 complex binds TRAF6, which regulates the ubiquitination of the IKK complex and NF-κB activation. p62 is required for the association of MEKK3 with TRAF6 and short hairpin RNA knockdown of p62 inhibits IL-1 and MEKK3 activation of NF-κB. The rear end acidic cluster of the p62 PB1 domain is used to organize cytosolic aggregates or speckles-associated TRAF6-p62-MEKK3 complex for control of NF-κB activation. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
| PLink | https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=egs&AN=48778360 |
| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1074/jbc.M109.065102 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 13 StartPage: 2077 Subjects: – SubjectFull: Scaffold proteins Type: general – SubjectFull: Protein kinase C Type: general – SubjectFull: RNA Type: general – SubjectFull: Osteitis deformans Type: general – SubjectFull: Luciferases Type: general – SubjectFull: Ligands (Biochemistry) Type: general Titles: – TitleFull: PB1 Domain Interaction of p62/Seq uestosome 1 and MEKK3 Regulates NF-κB Activation. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Nakamura, Kazuhiro – PersonEntity: Name: NameFull: Kimple, Adam J. – PersonEntity: Name: NameFull: Siderovski, David P. – PersonEntity: Name: NameFull: Johnson, Gary L. IsPartOfRelationships: – BibEntity: Dates: – D: 15 M: 01 Text: 1/15/2010 Type: published Y: 2010 Identifiers: – Type: issn-print Value: 00219258 Numbering: – Type: volume Value: 285 – Type: issue Value: 3 Titles: – TitleFull: Journal of Biological Chemistry Type: main |
| ResultId | 1 |
