CHD5 is a tumor suppressor at human 1p36.
Cancer gene discovery has relied extensively on analyzing tumors for gains and losses to reveal the location of oncogenes and tumor suppressor genes, respectively. Deletions of 1p36 are extremely common genetic lesions in human cancer, occurring in malignancies of epithelial, neural, and hematopoietic origin. Although this suggests that 1p36 harbors a gene that drives tumorigenesis when inactivated, the identity of this tumor suppressor has remained elusive. Here we use chromosome engineering to generate mouse models with gain and loss of a region corresponding to human 1p36. This approach functionally identifies chromodomain helicase DNA binding domain 5 (Chd5) as a tumor suppressor that controls proliferation, apoptosis, and senescence via the p19(Arf)/p53 pathway. We demonstrate that Chd5 functions as a tumor suppressor in vivo and implicate deletion of CHD5 in human cancer. Identification of this tumor suppressor provides new avenues for exploring innovative clinical interventions for cancer.
Bagchi
Anindya
A
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Papazoglu
Cristian
C
Wu
Ying
Y
Capurso
Daniel
D
Brodt
Michael
M
Francis
Dailia
D
Bredel
Markus
M
Vogel
Hannes
H
Mills
Alea A
AA
D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D033481:Chromosomes, Mammalian; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D004265:DNA Helicases / Q000235:genetics* / Q000378:metabolism; D018628:Gene Dosage; D020440:Gene Duplication; D016147:Genes, Tumor Suppressor; D005910:Glioma / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
C417743:Cdkn2a protein, mouse; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009419:Nerve Tissue Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D004265:DNA Helicases; C471926:CHD5 protein, human