Related Experiment Video

Updated: Jul 1, 2026

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells
09:24

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells

Published on: August 12, 2015

Glucose-regulated protein 78 as a novel effector of BRCA1 for inhibiting stress-induced apoptosis

B H Y Yeung1, B W Y Kwan, Q Y He

  • 1School of Biological Sciences, University of Hong Kong, Hong Kong, China.

Oncogene
|September 9, 2008
PubMed

Insights

The tumor suppressor BRCA1 regulates the unfolded protein response (UPR) by targeting glucose-regulated protein (GRP)-78. BRCA1 suppresses GRP78, impacting cancer cell survival and apoptosis.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cellular Biology

Background:

  • The tumor suppressor BRCA1 is frequently mutated in familial breast and ovarian cancers.
  • BRCA1's precise mechanisms of action are not fully understood.
  • The unfolded protein response (UPR) is crucial for cellular homeostasis and is implicated in cancer progression.

Purpose of the Study:

  • To investigate the relationship between BRCA1 and the UPR.
  • To identify GRP78 as a novel downstream target of BRCA1.
  • To elucidate BRCA1's role in regulating cancer cell survival and apoptosis via GRP78.

Main Methods:

  • Overexpression of wild-type and mutant BRCA1.
  • Small interfering RNA (siRNA) mediated knockdown of BRCA1 and GRP78.
  • Analysis of GRP78, GRP94, and CHOP expression.
  • Assessment of cell proliferation and apoptosis in ovarian (OVCAR-3) and breast (MCF-7) cancer cells.

Main Results:

  • Wild-type BRCA1 overexpression suppressed GRP78 expression, while BRCA1 inhibition enhanced it.
  • BRCA1 knockdown induced other UPR components (GRP94, CHOP).
  • Forced GRP78 expression promoted proliferation and inhibited apoptosis, whereas GRP78 knockdown sensitized cells to apoptosis.

Conclusions:

  • BRCA1 acts as a negative regulator of GRP78 expression.
  • BRCA1 influences cancer cell survival and apoptosis by modulating GRP78.
  • Targeting the BRCA1-GRP78 axis may offer therapeutic strategies for breast and ovarian cancers.

More Related Videos

Analysis of SCAP N-glycosylation and Trafficking in Human Cells11:27

Analysis of SCAP N-glycosylation and Trafficking in Human Cells

Published on: November 8, 2016

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Related Concept Videos

The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
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...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...