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GRWD1, a new player among oncogenesis-related ribosomal/nucleolar proteins

Takuya Takafuji1, Kota Kayama1, Nozomi Sugimoto1

  • 1a Department of Cellular Biochemistry, Graduate School of Pharmaceutical Sciences , Kyushu University , Higashi-ku, Fukuoka , Japan.

Cell Cycle (Georgetown, Tex.)
|July 20, 2017
PubMed

Insights

Certain ribosomal proteins can suppress or promote cancer. RPL5 and RPL11 inhibit tumor growth by regulating p53, while GRWD1 promotes it by sequestering RPL11, highlighting the complex role of ribosome proteins in oncogenesis.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • Ribosome biosynthesis-related proteins are increasingly implicated in oncogenesis.
  • Some ribosomal proteins, like RPL5 and RPL11, act as tumor suppressors by inhibiting MDM2 and up-regulating p53.
  • Conversely, other ribosomal proteins can promote tumorigenesis.

Purpose of the Study:

  • To investigate the dual role of ribosomal/nucleolar proteins in cancer.
  • To clarify the mechanisms by which these proteins influence tumorigenesis.
  • To identify novel factors involved in cancer development related to ribosome function.

Main Methods:

  • Analysis of ribosomal protein function in oncogenesis.
  • Investigation of protein-protein interactions (e.g., GRWD1 and RPL11).
  • Cellular transformation assays.

Main Results:

  • RPL5 and RPL11 prevent cancer by inhibiting MDM2 and stabilizing p53.
  • PICT1 promotes cancer by sequestering RPL11 in nucleoli, down-regulating p53.
  • GRWD1 overexpression suppresses p53 and transforms cells, likely by sequestering RPL11 from MDM2.

Conclusions:

  • Ribosome and nucleolar proteins have complex, context-dependent roles in cancer, acting as either tumor suppressors or promoters.
  • The p53 pathway is a key target for both tumor-suppressive and tumor-promoting ribosomal proteins.
  • Further research is needed to elucidate the full spectrum of ribosomal protein involvement in oncogenesis and identify potential therapeutic targets.
Keywords:
GRWD1PICT1RPL11nucleolar stress responseoncogenep53tumor suppressor

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