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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...
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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.
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...
DNA Damage Can Stall the Cell Cycle02:36

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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...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

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Yeast As a Chassis for Developing Functional Assays to Study Human P53
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Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

Redefining the p53 response element.

Bei Wang1, Ziwei Xiao, Ee Chee Ren

  • 1Laboratory of Immunogenetics, Singapore Immunology Network, A*STAR, 8A Biomedical Grove, Immunos, Singapore.

Proceedings of the National Academy of Sciences of the United States of America
|July 15, 2009
PubMed
Summary
This summary is machine-generated.

The tumor suppressor p53

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Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • The tumor suppressor p53 is a critical regulator of cellular events.
  • Predicting p53's transcriptional effects on target genes remains challenging despite numerous identified response elements (REs).

Purpose of the Study:

  • To systematically investigate the role of specific nucleotides within p53 REs.
  • To establish predictive rules for p53's transcriptional activation or repression.
  • To re-evaluate known p53 RE functions.

Main Methods:

  • Functional assays using p21 (activation) and Lasp1 (repression) targets.
  • Analysis of nucleotide sequences within the p53 RE, focusing on the CWWG motif and flanking regions.
  • Reassessment of 162 published p53 REs based on newly established rules.

Main Results:

  • A specific dinucleotide core within the CWWG motif dictates p53's activation or repression.
  • Flanking RRR and YYY triplets modulate p53 transcriptional activity.
  • 20/162 previously studied p53 REs were found to have erroneous functional attributions.
  • 39/162 p53 REs exhibit repressive functions, a higher proportion than previously recognized.

Conclusions:

  • Nucleotide sequence within p53 REs precisely determines transcriptional outcome (activation vs. repression).
  • Established predictive rules offer enhanced understanding of p53's role in cellular networks.
  • The prevalence of p53-mediated gene repression is significantly underestimated.