Integration of DNA damage and repair with murine double-minute 2 (Mdm2) in tumorigenesis

The alteration of tumorigenic pathways leading to cancer is a degenerative disease process typically involving inactivation of tumor suppressor proteins and hyperactivation of oncogenes. One such oncogenic protein product is the murine double-minute 2, or Mdm2. While, Mdm2 has been primarily associa...

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Published inInternational journal of molecular sciences Vol. 13; no. 12; pp. 16373 - 16386
Main Authors Lehman, Jason A, Mayo, Lindsey D
Format Journal Article Book Review
LanguageEnglish
Published Switzerland MDPI AG 03.12.2012
Molecular Diversity Preservation International (MDPI)
Subjects
Animals
Base excision repair
Cancer
Carcinogenesis - genetics
Chemotherapy
DNA damage
DNA Damage - genetics
DNA Mismatch Repair
DNA repair
DNA Repair - genetics
genomics
Homologous Recombination
Humans
Integration
MDM2 protein
mismatch repair
murine double minute-2
Non-homologous end joining
Nucleotide excision repair
Oncogenes
p53 protein
Proto-Oncogene Proteins c-mdm2 - physiology
Review
Signal Transduction - genetics
Tumor suppressor genes
Tumorigenesis
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Abstract The alteration of tumorigenic pathways leading to cancer is a degenerative disease process typically involving inactivation of tumor suppressor proteins and hyperactivation of oncogenes. One such oncogenic protein product is the murine double-minute 2, or Mdm2. While, Mdm2 has been primarily associated as the negative regulator of the p53 tumor suppressor protein there are many p53-independent roles demonstrated for this oncogene. DNA damage and chemotherapeutic agents are known to activate Mdm2 and DNA repair pathways. There are five primary DNA repair pathways involved in the maintenance of genomic integrity: Nucleotide excision repair (NER), Base excision repair (BER), Mismatch repair (MMR), Non-homologous end joining (NHEJ) and homologous recombination (HR). In this review, we will briefly describe these pathways and also delineate the functional interaction of Mdm2 with multiple DNA repair proteins. We will illustrate the importance of these interactions with Mdm2 and discuss how this is important for tumor progression, cellular proliferation in cancer.
AbstractList The alteration of tumorigenic pathways leading to cancer is a degenerative disease process typically involving inactivation of tumor suppressor proteins and hyperactivation of oncogenes. One such oncogenic protein product is the murine double-minute 2, or Mdm2. While, Mdm2 has been primarily associated as the negative regulator of the p53 tumor suppressor protein there are many p53-independent roles demonstrated for this oncogene. DNA damage and chemotherapeutic agents are known to activate Mdm2 and DNA repair pathways. There are five primary DNA repair pathways involved in the maintenance of genomic integrity: Nucleotide excision repair (NER), Base excision repair (BER), Mismatch repair (MMR), Non-homologous end joining (NHEJ) and homologous recombination (HR). In this review, we will briefly describe these pathways and also delineate the functional interaction of Mdm2 with multiple DNA repair proteins. We will illustrate the importance of these interactions with Mdm2 and discuss how this is important for tumor progression, cellular proliferation in cancer.
Author Lehman, Jason A
Mayo, Lindsey D
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SSID ssj0023259
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SecondaryResourceType review_article
Snippet The alteration of tumorigenic pathways leading to cancer is a degenerative disease process typically involving inactivation of tumor suppressor proteins and...
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StartPage 16373
SubjectTerms Animals
Base excision repair
Cancer
Carcinogenesis - genetics
Chemotherapy
DNA damage
DNA Damage - genetics
DNA Mismatch Repair
DNA repair
DNA Repair - genetics
genomics
Homologous Recombination
Humans
Integration
MDM2 protein
mismatch repair
murine double minute-2
Non-homologous end joining
Nucleotide excision repair
Oncogenes
p53 protein
Proto-Oncogene Proteins c-mdm2 - physiology
Review
Signal Transduction - genetics
Tumor suppressor genes
Tumorigenesis
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Title Integration of DNA damage and repair with murine double-minute 2 (Mdm2) in tumorigenesis
URI https://www.ncbi.nlm.nih.gov/pubmed/23208375
https://www.proquest.com/docview/1526013696
https://search.proquest.com/docview/1315626656
https://pubmed.ncbi.nlm.nih.gov/PMC3546695
https://doaj.org/article/e901dd602e904dea828d02d61f136054
Volume 13
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