GW112, a novel antiapoptotic protein that promotes tumor growth

Xiuwu Zhang1, Qian Huang, Zhonghui Yang

  • 1Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710, USA.

Cancer Research
|April 3, 2004
PubMed

Insights

The novel gene GW112 inhibits apoptosis, promoting tumor cell survival and growth. It counteracts GRIM-19

Area of Science:

  • Molecular Biology
  • Oncology
  • Cell Death Research

Background:

  • GW112 is a novel gene with limited homology to known genes.
  • GW112 is overexpressed in various human tumors, particularly digestive system cancers.
  • GRIM-19 is a known regulator of cellular apoptosis.

Purpose of the Study:

  • To investigate the role of GW112 in apoptosis regulation.
  • To determine GW112's functional interaction with GRIM-19.
  • To assess GW112's impact on tumor cell survival and growth.

Main Methods:

  • Co-immunoprecipitation to study GW112 and GRIM-19 association.
  • Apoptosis assays in tumor cells treated with retinoic acid, IFN-beta, and hydrogen peroxide.
  • In vivo tumor formation studies using GW112-overexpressing murine prostate tumor cells.

Main Results:

  • GW112 associates with GRIM-19.
  • GW112 attenuates GRIM-19-mediated apoptosis induced by retinoic acid and IFN-beta.
  • GW112 exhibits antiapoptotic effects against hydrogen peroxide-induced stress.
  • Overexpression of GW112 accelerates tumor formation in vivo.

Conclusions:

  • GW112 is a novel regulator of apoptosis.
  • GW112 promotes tumor cell survival and growth by inhibiting cell death pathways.
  • GW112 represents a potential therapeutic target in cancer treatment.

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...
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...
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...
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...
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...
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,...