The secreted glycoprotein CREG inhibits cell growth dependent on the mannose-6-phosphate/insulin-like growth factor

Alessandra Di Bacco1, Grace Gill

  • 1Department of Pathology, Harvard Medical School, 200 Longwood Ave., Boston, MA 02115, USA.

Oncogene
|August 23, 2003
PubMed

Insights

Cellular repressor of E1A-stimulated genes (CREG) inhibits cell growth by binding to the mannose-6-phosphate/insulin-like growth factor II receptor (M6P/IGF2R), a tumor suppressor. This interaction is crucial for CREG

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Secreted proteins and receptors regulate cell functions like proliferation and differentiation.
  • Cellular repressor of E1A-stimulated genes (CREG) antagonizes cellular transformation and promotes neuronal differentiation.
  • Mannose-6-phosphate/insulin-like growth factor II receptor (M6P/IGF2R) is a tumor suppressor involved in cell growth control.

Purpose of the Study:

  • To investigate the mechanism of CREG-induced growth inhibition.
  • To determine the role of M6P/IGF2R in CREG's function.
  • To explore the interaction between CREG and M6P/IGF2R.

Main Methods:

  • Ectopic expression of CREG in NTERA-2 cells.
  • Cell cycle analysis to assess G1/S phase transition.
  • Assays to study CREG binding to M6P/IGF2R, including glycosylation dependence.
  • Analysis of CREG activity in M6P/IGF2R-deficient cells.

Main Results:

  • Ectopic CREG expression caused cell cycle delay at G1/S and growth inhibition.
  • CREG directly binds to M6P/IGF2R in a glycosylation-dependent manner.
  • M6P/IGF2R is essential for CREG-induced growth inhibition.

Conclusions:

  • CREG inhibits cell growth through a mechanism dependent on M6P/IGF2R.
  • The interaction between CREG and M6P/IGF2R suggests a role in regulating proliferation and differentiation.
  • CREG and M6P/IGF2R may collaborate in controlling cell growth across various lineages.

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
Insulin: The Receptor and Signaling Pathways01:28

Insulin: The Receptor and Signaling Pathways

Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but this inhibition is released...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...