title: The role of RAD9 in tumorigenesis.
abstract: RAD9 regulates multiple cellular processes that influence genomic integrity, and for at least some of its functions the protein acts as part of a heterotrimeric complex bound to HUS1 and RAD1 proteins. RAD9 participates in DNA repair, including base excision repair, homologous recombination repair and mismatch repair, multiple cell cycle phase checkpoints and apoptosis. In addition, functions including the transactivation of downstream target genes, immunoglobulin class switch recombination, as well as 3'-5' exonuclease activity have been reported. Aberrant RAD9 expression has been linked to breast, lung, thyroid, skin and prostate tumorigenesis, and a cause-effect relationship has been demonstrated for the latter two. Interestingly, human RAD9 overproduction correlates with prostate cancer whereas deletion of Mrad9, the corresponding mouse gene, in keratinocytes leads to skin cancer. These results reveal that RAD9 protein can function as an oncogene or tumor suppressor, and aberrantly high or low levels can have deleterious health consequences. It is not clear which of the many functions of RAD9 is critical for carcinogenesis, but several alternatives are considered herein and implications for the development of novel cancer therapies based on these findings are examined.
authors.affiliation: Center for Radiological Research, Columbia University College of Physicians and Surgeons, 630 W 168th St, New York, NY 10032, USA. hbl1@columbia.edu
authors.forename: Howard B
authors.initials: HB
authors.lastname: Lieberman
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Bernstock
authors.forename: Constantinos G
authors.initials: CG
authors.lastname: Broustas
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Hopkins
authors.forename: Corinne
authors.initials: C
authors.lastname: Leloup
authors.forename: Aiping
authors.initials: A
authors.lastname: Zhu
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004249:DNA Damage; D004260:DNA Repair; D005090:Exodeoxyribonucleases; D016147:Genes, Tumor Suppressor; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000209:etiology* / Q000235:genetics / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; C069930:rad9 protein; D005090:Exodeoxyribonucleases