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Hipk2 cooperates with p53 to suppress γ-ray radiation-induced mouse thymic lymphoma

Journal Article · · Oncogene
DOI:https://doi.org/10.1038/onc.2011.306· OSTI ID:1624017
 [1];  [2];  [2];  [2];  [3];  [2];  [2];  [2];  [2];  [4];  [2]
  1. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Division; DOE/OSTI
  2. Helen Diller Family Comprehensive Cancer Center, San Francisco, CA (United States)
  3. Univ. of California, San Francisco, CA (United States). Dept. of Pathology; Shandong Univ., Jinan (China). School of Medicine
  4. Univ. of California, San Francisco, CA (United States). Dept. of Pathology
+ Show Author Affiliations
A genome-wide screen for genetic alterations in radiation-induced thymic lymphomas generated from p53 þ / and p53/ mice showed frequent loss of heterozygosity (LOH) on chromosome 6. Fine mapping of these LOH regions revealed three non-overlapping regions, one of which was refined to a 0.2Mb interval that contained only the gene encoding homeobox-interacting protein kinase 2 (Hipk2). More than 30% of radiation-induced tumors from both p53 þ / and p53/ mice showed heterozygous loss of one Hipk2 allele. Mice carrying a single inactive allele of Hipk2 in the germline were susceptible to induction of tumors by c-radiation, but most tumors retained and expressed the wild-type allele, suggesting that Hipk2 is a haploin-sufficient tumor suppressor gene for mouse lymphoma development. Heterozygous loss of both Hipk2 and p53 confers strong sensitization to radiation-induced lymphoma. We conclude that Hipk2 is a haploin-sufficient lymphoma suppressor gene.
Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
Grant/Contract Number:
AC02-05CH11231; FG02-03ER63630
OSTI ID:
1624017
Journal Information:
Oncogene, Journal Name: Oncogene Journal Issue: 9 Vol. 31; ISSN 0950-9232
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
English

References (20)

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Cited By (17)

HIPK2 catalytic activity and subcellular localization are regulated by activation-loop Y354 autophosphorylation journal June 2013
HIPK2 restricts SIRT1 activity upon severe DNA damage by a phosphorylation-controlled mechanism journal June 2015
Glucose restriction induces cell death in parental but not in homeodomain-interacting protein kinase 2-depleted RKO colon cancer cells: molecular mechanisms and implications for tumor therapy journal May 2013
Role of HIPK2 in kidney fibrosis journal November 2014
The nutrient sensor OGT regulates Hipk stability and tumorigenic-like activities in Drosophila journal January 2020
Response of mouse thymic cells to radiation after transfusion of mesenchymal stem cells journal December 2016
Tumor suppressive role for kinases phosphorylating p53 in DNA damage-induced apoptosis journal October 2018
Updates on HIPK2: a resourceful oncosuppressor for clearing cancer journal August 2012
Targeting COX-2/PGE2 Pathway in HIPK2 Knockdown Cancer Cells: Impact on Dendritic Cell Maturation journal November 2012
HIPK2 deficiency causes chromosomal instability by cytokinesis failure and increases tumorigenicity journal March 2015
ShaPINg Cell Fate Upon DNA Damage: Role of Pin1 Isomerase in DNA Damage-Induced Cell Death and Repair journal June 2014
HIPK2 is a new drug target for anti-fibrosis therapy in kidney disease journal April 2015
HIPK2: A tumour suppressor that controls DNA damage-induced cell fate and cytokinesis journal November 2012
Posttranslational modifications regulate HIPK2, a driver of proliferative diseases journal April 2013
HIPK2 kinase activity depends on cis-autophosphorylation of its activation loop journal February 2013
Verbascoside promotes apoptosis by regulating HIPK2–p53 signaling in human colorectal cancer journal October 2014
Src kinase modulates the apoptotic p53 pathway by altering HIPK2 localization journal October 2013

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