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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.
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
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Co-activators and Co-repressors02:04

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Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
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Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
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.

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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

The NF-Y/p53 liaison: well beyond repression.

Carol Imbriano1, Nerina Gnesutta, Roberto Mantovani

  • 1Dipartimento di Biologia, Università degli Studi di Modena e Reggio Emilia, Via Campi 213/d, 41100 Modena, Italy.

Biochimica Et Biophysica Acta
|December 6, 2011
PubMed
Summary

The transcription factor NF-Y interacts with p53, influencing cell survival and death pathways, particularly under DNA-damage conditions. This interaction is critical for regulating gene expression and cellular responses to stress.

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Purification of Ubiquitinated p53 Proteins from Mammalian Cells
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Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Published on: March 21, 2022

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cellular Signaling

Background:

  • NF-Y is a transcription factor that binds to the CCAAT promoter element.
  • p53 is a key transcription factor regulating cellular responses to DNA damage and genomic instability, frequently altered in cancer.
  • The interplay between NF-Y and p53 (and related proteins p63, p73) impacts gene expression under DNA-damage conditions.

Purpose of the Study:

  • To elucidate the role of the NF-Y/p53 interaction in cellular fate determination.
  • To investigate how DNA damage and specific p53 mutations affect this interaction and downstream gene regulation.
  • To explore the involvement of NF-Y in pro-apoptotic activities, including mediation of p53 transcriptional activation and regulation by non-coding RNA PANDA.

Main Methods:

  • Analysis of transcriptional repression of NF-Y target genes under DNA-damage conditions.
  • Investigation of NF-Y's direct and indirect roles in apoptosis.
  • Examination of interactions between NF-Y, p53, p63, p73, TopBP1, and PANDA in various cellular contexts, including those with mutant p53.

Main Results:

  • The NF-Y/p53 interaction mediates transcriptional repression of specific genes in response to DNA damage.
  • NF-Y participates in pro-apoptotic functions, either through p53 activation or via regulation by PANDA.
  • Gain-of-function mutant p53, interacting with TopBP1, alters the cellular response, subverting normal NF-Y/p53 pathway functions.

Conclusions:

  • The intricate connection between p53 and NF-Y is a critical determinant of cell survival versus cell death.
  • Dysregulation of the NF-Y/p53 axis, particularly in the context of mutant p53 and DNA repair proteins, has significant implications for cancer.
  • Understanding these molecular interactions provides insights into therapeutic strategies targeting cancer cell fate.