Growth inhibitory effects of large subunit ribosomal proteins in melanoma

Gregory R. Kardos, Mushui Dai, Gavin P. Robertson

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)801-812
Number of pages12
JournalPigment Cell and Melanoma Research
Volume27
Issue number5
DOIs
StatePublished - 2014

Fingerprint

Ribosomal Proteins
Melanoma
Cell Proliferation
Protein Biosynthesis
Growth
Cell Survival
Proteins
Cells
Cell proliferation
Neoplasms
Tumors
Cell Cycle Checkpoints
Ribosomes
Small Interfering RNA
Stabilization
Modulation
Degradation
Therapeutics

Keywords

  • Cell cycle
  • Melanoma
  • P53
  • Protein synthesis
  • Ribosomal proteins
  • RP-MDM2-p53

ASJC Scopus subject areas

  • Dermatology
  • Oncology
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Growth inhibitory effects of large subunit ribosomal proteins in melanoma. / Kardos, Gregory R.; Dai, Mushui; Robertson, Gavin P.

In: Pigment Cell and Melanoma Research, Vol. 27, No. 5, 2014, p. 801-812.

Research output: Contribution to journalArticle

Kardos, Gregory R. ; Dai, Mushui ; Robertson, Gavin P. / Growth inhibitory effects of large subunit ribosomal proteins in melanoma. In: Pigment Cell and Melanoma Research. 2014 ; Vol. 27, No. 5. pp. 801-812.
@article{65e5d512055a40009b24129d84282c88,
title = "Growth inhibitory effects of large subunit ribosomal proteins in melanoma",
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.",
keywords = "Cell cycle, Melanoma, P53, Protein synthesis, Ribosomal proteins, RP-MDM2-p53",
author = "Kardos, {Gregory R.} and Mushui Dai and Robertson, {Gavin P.}",
year = "2014",
doi = "10.1111/pcmr.12259",
language = "English (US)",
volume = "27",
pages = "801--812",
journal = "Pigment Cell and Melanoma Research",
issn = "1755-1471",
publisher = "Wiley-Blackwell",
number = "5",

}

TY - JOUR

T1 - Growth inhibitory effects of large subunit ribosomal proteins in melanoma

AU - Kardos, Gregory R.

AU - Dai, Mushui

AU - Robertson, Gavin P.

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - Cell cycle

KW - Melanoma

KW - P53

KW - Protein synthesis

KW - Ribosomal proteins

KW - RP-MDM2-p53

UR - http://www.scopus.com/inward/record.url?scp=84907971217&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84907971217&partnerID=8YFLogxK

U2 - 10.1111/pcmr.12259

DO - 10.1111/pcmr.12259

M3 - Article

VL - 27

SP - 801

EP - 812

JO - Pigment Cell and Melanoma Research

JF - Pigment Cell and Melanoma Research

SN - 1755-1471

IS - 5

ER -