View in EDS

A Cytosolic Multiprotein Complex Containing p85α Is Required for β-Catenin Activation in Colitis and Colitis-associated Cancer.

Saved in:
Bibliographic Details
Title: A Cytosolic Multiprotein Complex Containing p85α Is Required for β-Catenin Activation in Colitis and Colitis-associated Cancer.
Authors: Goretsky, Tatiana1, Bradford, Emily M.1, Hyunji Ryu2, Tahir, Maryam1, Moyer, Mary Pat3, Tianyan Gao4, Linheng Li5, Barrett, Terrence A.1 t.barrett@uky.edu
Source: Journal of Biological Chemistry. 2/19/2016, Vol. 291 Issue 8, p4166-4177. 12p.
Subjects: Colitis, Intestines, Epithelial cells, Carcinogenesis, Patients
Abstract: Wnt/β-catenin signaling is required for crypt structure maintenance. We previously observed nuclear accumulation of Ser- 552 phosphorylated β-catenin (pβ-CatSer-552) in intestinal epithelial cells (IEC) during colitis and colitis-associated cancer. Data here delineate a novel multiprotein cytosolic complex (MCC) involved in β-catenin signaling in the intestine. The MCC contains p85α, the class IA subunit of PI3K, along with β-catenin, 14-3-3ζ, Akt, and p110α. MCC levels in IEC increase in colitis and colitis-associated cancer patients. IEC-specific p85α-deficient (p85ΔIEC) mice develop more severe dextran sodium sulfate colitis due to delayed ulcer healing and reduced epithelial β-catenin activation. In colonic IEC, p85α deficiency did not alter PI3K signaling. In vitro shRNA depletion of individual complex members disrupts the MCC and reduces β- catenin signaling. Despite worse colitis, p85ΔIEC mice have reduced tumor burden after azoxymethane/dextran sodium sulfate treatment. Together the data indicate that the β-catenin MCC is needed for mucosal repair and carcinogenesis. This novel MCC may be an attractive therapeutic target in preventing cancer in colitis patients. [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: 113221772
AccessLevel: 6
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 0
IllustrationInfo
Items – Name: Title
  Label: Title
  Group: Ti
  Data: A Cytosolic Multiprotein Complex Containing p85α Is Required for β-Catenin Activation in Colitis and Colitis-associated Cancer.
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AR" term="%22Goretsky%2C+Tatiana%22">Goretsky, Tatiana</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Bradford%2C+Emily+M%2E%22">Bradford, Emily M.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Hyunji+Ryu%22">Hyunji Ryu</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Tahir%2C+Maryam%22">Tahir, Maryam</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Moyer%2C+Mary+Pat%22">Moyer, Mary Pat</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Tianyan+Gao%22">Tianyan Gao</searchLink><relatesTo>4</relatesTo><br /><searchLink fieldCode="AR" term="%22Linheng+Li%22">Linheng Li</searchLink><relatesTo>5</relatesTo><br /><searchLink fieldCode="AR" term="%22Barrett%2C+Terrence+A%2E%22">Barrett, Terrence A.</searchLink><relatesTo>1</relatesTo><i> t.barrett@uky.edu</i>
– Name: TitleSource
  Label: Source
  Group: Src
  Data: <searchLink fieldCode="JN" term="%22Journal+of+Biological+Chemistry%22">Journal of Biological Chemistry</searchLink>. 2/19/2016, Vol. 291 Issue 8, p4166-4177. 12p.
– Name: Subject
  Label: Subjects
  Group: Su
  Data: <searchLink fieldCode="DE" term="%22Colitis%22">Colitis</searchLink><br /><searchLink fieldCode="DE" term="%22Intestines%22">Intestines</searchLink><br /><searchLink fieldCode="DE" term="%22Epithelial+cells%22">Epithelial cells</searchLink><br /><searchLink fieldCode="DE" term="%22Carcinogenesis%22">Carcinogenesis</searchLink><br /><searchLink fieldCode="DE" term="%22Patients%22">Patients</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Wnt/β-catenin signaling is required for crypt structure maintenance. We previously observed nuclear accumulation of Ser- 552 phosphorylated β-catenin (pβ-CatSer-552) in intestinal epithelial cells (IEC) during colitis and colitis-associated cancer. Data here delineate a novel multiprotein cytosolic complex (MCC) involved in β-catenin signaling in the intestine. The MCC contains p85α, the class IA subunit of PI3K, along with β-catenin, 14-3-3ζ, Akt, and p110α. MCC levels in IEC increase in colitis and colitis-associated cancer patients. IEC-specific p85α-deficient (p85ΔIEC) mice develop more severe dextran sodium sulfate colitis due to delayed ulcer healing and reduced epithelial β-catenin activation. In colonic IEC, p85α deficiency did not alter PI3K signaling. In vitro shRNA depletion of individual complex members disrupts the MCC and reduces β- catenin signaling. Despite worse colitis, p85ΔIEC mice have reduced tumor burden after azoxymethane/dextran sodium sulfate treatment. Together the data indicate that the β-catenin MCC is needed for mucosal repair and carcinogenesis. This novel MCC may be an attractive therapeutic target in preventing cancer in colitis patients. [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=113221772
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1074/jbc.M115.669416
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 12
        StartPage: 4166
    Subjects:
      – SubjectFull: Colitis
        Type: general
      – SubjectFull: Intestines
        Type: general
      – SubjectFull: Epithelial cells
        Type: general
      – SubjectFull: Carcinogenesis
        Type: general
      – SubjectFull: Patients
        Type: general
    Titles:
      – TitleFull: A Cytosolic Multiprotein Complex Containing p85α Is Required for β-Catenin Activation in Colitis and Colitis-associated Cancer.
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Goretsky, Tatiana
      – PersonEntity:
          Name:
            NameFull: Bradford, Emily M.
      – PersonEntity:
          Name:
            NameFull: Hyunji Ryu
      – PersonEntity:
          Name:
            NameFull: Tahir, Maryam
      – PersonEntity:
          Name:
            NameFull: Moyer, Mary Pat
      – PersonEntity:
          Name:
            NameFull: Tianyan Gao
      – PersonEntity:
          Name:
            NameFull: Linheng Li
      – PersonEntity:
          Name:
            NameFull: Barrett, Terrence A.
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 19
              M: 02
              Text: 2/19/2016
              Type: published
              Y: 2016
          Identifiers:
            – Type: issn-print
              Value: 00219258
          Numbering:
            – Type: volume
              Value: 291
            – Type: issue
              Value: 8
          Titles:
            – TitleFull: Journal of Biological Chemistry
              Type: main
ResultId 1