Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Pigment Cell Melanoma Res. 2014 Sep;27(5):801-12. doi: 10.1111/pcmr.12259. Epub 2014 Jun 16.

Growth inhibitory effects of large subunit ribosomal proteins in melanoma.

Author information

  • 1Department of Pharmacology, The Pennsylvania State University College of Medicine, Hershey, PA, USA; The Melanoma Center, The Pennsylvania State University College of Medicine, Hershey, PA, USA; The Melanoma Therapeutics Program, The Pennsylvania State University College of Medicine, Hershey, PA, USA.

Abstract

Ribosome biogenesis can modulate protein synthesis, a process heavily relied upon for cancer cell proliferation. In this study, involvement of large subunit ribosomal proteins (RPLs) in melanoma has been dissected and RPLs categorized based on modulation of cell proliferation and therapeutic targeting potential. Based on these results, two categories of RPLs were identified: the first causing negligible effects on cell viability, p53 expression, and protein translation, while the second category decreased cell viability and inhibited protein synthesis mediated with or without p53 protein stabilization. RPL13 represents the second category, where siRNA-mediated targeting inhibited tumor development through decreased cellular proliferation. Mechanistically, decreased RPL13 levels increased p53 stability mediated by RPL5 and RPL11 binding to and preventing MDM2 from targeting p53 for degradation. The consequence was p53-dependent cell cycle arrest and decreased protein translation. Thus, targeting certain category 2 RPL proteins can inhibit melanoma tumor development mediated through the MDM2-p53 pathway.

© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

KEYWORDS:

RP-MDM2-p53; cell cycle; melanoma; p53; protein synthesis; ribosomal proteins

PMID:
24807543
[PubMed - in process]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Blackwell Publishing
    Loading ...
    Write to the Help Desk