Sgk1 enhances RANBP1 transcript levels and decreases taxol sensitivity in RKO colon carcinoma cells

R Amato1, D Scumaci, L D'Antona

  • 1Department of Human Health, University Magna Graecia at Catanzaro, Campus S Venuta, Località Germaneto Viale Europa, Catanzaro, Italy.

Oncogene
|October 31, 2012
PubMed

Insights

Serum- and glucocorticoid-regulated kinase (Sgk1) impacts cancer cell proliferation by regulating RAN-binding protein 1 (RANBP1). This Sgk1-RANBP1 interaction affects microtubule activity and taxol sensitivity in cancer cells.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • Serum- and glucocorticoid-regulated kinase (Sgk1) plays a crucial role in hormonal regulation of sodium transport and cell signaling.
  • Sgk1 is increasingly recognized as a significant factor in human cancer development and progression.
  • Understanding Sgk1's role in cell proliferation is vital for cancer research.

Purpose of the Study:

  • To investigate the molecular mechanisms by which Sgk1 influences cancer cell proliferation.
  • To identify proteins regulated by Sgk1 using a proteomic approach.
  • To elucidate the functional consequences of Sgk1-mediated regulation of specific proteins.

Main Methods:

  • Utilized Sgk1-specific RNA silencing to identify differentially expressed proteins.
  • Employed a proteomic approach to analyze protein abundance changes.
  • Focused on RAN-binding protein 1 (RANBP1) as a key Sgk1-regulated protein.

Main Results:

  • Identified several proteins, including RANBP1, that are up- or downregulated upon Sgk1 silencing.
  • Demonstrated that Sgk1 regulates the abundance of RANBP1, a major effector of the GTPase RAN.
  • Showed that Sgk1-dependent regulation of RANBP1 impacts mitotic microtubule activity.

Conclusions:

  • Sgk1-mediated regulation of RANBP1 has functional implications for cancer cell biology.
  • The Sgk1-RANBP1 pathway influences cancer cell sensitivity to taxol, a chemotherapeutic agent.
  • This study provides new insights into Sgk1's role in cancer progression and potential therapeutic targets.

Related Concept Videos

The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Directionality of Nuclear Transport01:42

Directionality of Nuclear Transport

Ras-related nuclear protein or Ran is a small G protein that cycles between its GTP and GDP bound states. Ran specific regulators, a Ran GTPase Activating Protein or RanGAP present in the cytosol and a Ran guanine nucleotide exchange factor or RanGEF present inside the nucleus regulate GTP/GDP exchange. A high concentration of GTP inside the cells, in addition to this asymmetric distribution of  Ran-specific regulators, leads to a higher RanGTP concentration inside the nucleus. This...
Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...