A novel p53-inducible gene, PAG608, encodes a nuclear zinc finger protein whose overexpression promotes apoptosis

D Israeli1, E Tessler, Y Haupt

  • 1Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot, Israel.

The EMBO Journal
|July 16, 1997
PubMed

Insights

Researchers identified PAG608, a novel gene induced by DNA damage in a p53-dependent manner. This p53 target gene encodes a nuclear protein that promotes apoptosis and may mediate p53’s tumor suppressor functions.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • The p53 tumor suppressor protein regulates cellular responses to DNA damage.
  • p53 exerts its functions by transactivating specific target genes.
  • Identifying novel p53 target genes is crucial for understanding p53-mediated biological effects, including apoptosis.

Purpose of the Study:

  • To identify novel p53 target genes involved in p53-mediated apoptosis.
  • To characterize a newly discovered p53-inducible gene, PAG608.

Main Methods:

  • Differential display method was used to identify novel p53 target genes.
  • PAG608 gene expression was analyzed in response to DNA damage.
  • PAG608 protein localization and functional effects were assessed in transfected human tumor cells.

Main Results:

  • A novel p53-inducible gene, PAG608, was identified.
  • PAG608 transcripts are upregulated by DNA damage in a p53-dependent manner.
  • PAG608 encodes a nuclear zinc finger protein that localizes to nucleoli and promotes apoptosis upon overexpression.

Conclusions:

  • PAG608 is a novel p53 target gene induced by DNA damage.
  • PAG608 may contribute to p53-mediated apoptosis and its tumor suppressor activities.

Related Concept Videos

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.
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
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...
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...
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...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...