Science exchange logo white
  • Solutions
      Buyers

      We are making R&D services readily available to every organization that seeks to make scientific impact. Learn More

      Providers

      We are changing the way providers access and engage customers to streamline the sale and delivery of R&D services. Learn More

      Industries Agriscience Animal Health Basic Research Biopharmaceutical Chemicals Consumer Health Food Science Medical Devices
      Reproducibility

      We believe that good experiments can and should be independently replicated and validated. Learn More

  • Resources
    Innovation Blog
    Customer Stories
    Events
    Industry Trends
    News
    Product Updates
    Help Center
  • About
    About
    Our Story
    Leadership
    Partners
    Join the Team
  • Contact
  • Log In Sign Up
  • Get a Demo
  • Role of p12(CDK2-AP1) in transforming growth factor-beta1-mediated growth suppression.

    Cancer Res. 64(2):490-9. January 15, 2004. View on PubMed.
  • Authors

    Hu MG, Hu GF, Kim Y, Tsuji T, McBride J, Hinds P, and Wong DT
  • Abstract

    p12(CDK2-AP1) (p12) is a growth suppressor isolated from normal keratinocytes. Ectopic expression of p12 in squamous carcinoma cells reversed the malignant phenotype of these cells, in part due an ability of p12 to bind to both DNA polymerase alpha/primase and to cyclin-dependent kinase 2 (CDK2), thereby inhibiting their activities. We report in this article that in normal epithelial cells, transforming growth factor beta1 (TGF-beta1) induces p12 expression transcriptionally, which, in turn, mediates the growth inhibitory activity of TGF-beta1. We created inducible p12 antisense HaCaT cell lines [ip12 (-) HaCaT] and showed that selective reduction of cellular p12 resulted in an increase in (a) CDK2-associated kinase activity; (b) protein retinoblastoma (pRB) phosphorylation; and (c) [(3)H]thymidine incorporation, and partially reversed TGF-beta1-mediated inhibition of CDK2 kinase activity, pRB phosphorylation, and cell proliferation. Furthermore, we generated p12-deficient mouse oral keratinocytes (MOK(p12-/-)) and compared their growth characteristics and response to TGF-beta1 with that of wild-type mouse oral keratinocytes (MOK(WT)). Under normal culture conditions, the number of MOK(p12-/-) in S phase is 2-fold greater than that of MOK(WT). Concomitantly, fewer cells are in G(2) phase in MOK(p12-/-) than that in MOK(WT). Moreover, response to TGF-beta1-mediated growth suppression is compromised in MOK(p12-/-) cells. Mechanistic studies showed that MOK(p12-/-) have increased CDK2 activity and reduced sensitivity to inhibition by TGF-beta1. Collectively our data suggest that p12 plays a role in TGF-beta1-mediated growth suppression by modulating CDK2 activities and pRB phosphorylation.

Science exchange logo white

  • Facebook
  • Twitter
  • LinkedIn

Solutions

  • Buyers
  • Providers
  • Reproducibility

Industries

  • Agriscience
  • Animal Health
  • Basic Research
  • Biopharmaceutical
  • Chemicals
  • Consumer Health
  • Food Science
  • Medical Devices

Resources

  • Innovation Blog
  • Customer Stories
  • Events
  • Industry Trends
  • News
  • Product Updates

About

  • Our Story
  • Leadership
  • Partners
  • Join the Team

Support

  • Contact Us
  • Help Center
  • Trust
  • Terms of Use
  • Privacy Policy

Copyright © 2021 Science Exchange, Inc. All rights reserved.