| First Author | Yin Z | Year | 2012 |
| Journal | Cancer Res | Volume | 72 |
| Issue | 19 | Pages | 5080-90 |
| PubMed ID | 22896338 | Mgi Jnum | J:191827 |
| Mgi Id | MGI:5463171 | Doi | 10.1158/0008-5472.CAN-12-1484 |
| Citation | Yin Z, et al. (2012) RAP80 is critical in maintaining genomic stability and suppressing tumor development. Cancer Res 72(19):5080-90 |
| abstractText | The ubiquitin interaction motif-containing protein RAP80 was recently found to play a key role in DNA damage response (DDR) signaling by facilitating the translocation of several DDR mediators, including BRCA1, to ionizing irradiation (IR)-induced foci. In this study, we examine the effect of the loss of RAP80 on genomic stability and the susceptibility to cancer development in RAP80 null (RAP80(-/-)) mice. RAP80(-/-) mice are viable and did not exhibit any apparent developmental defects. Mouse embryonic fibroblasts (MEF) derived from RAP80(-/-) mice underwent premature senescence compared with wild-type (WT) MEFs, were more sensitive to IR, and exhibited a higher level of spontaneous and IR-induced genomic instability. RAP80(-/-) thymocytes were more sensitive to IR-induced cell death than WT thymocytes. RAP80(-/-) mice were more susceptible to spontaneous lymphoma development and the development of 7,12-dimethylbenz(a)anthracene-induced mammary gland tumors. Moreover, the loss of RAP80 accelerated tumor formation in both p53(-/-) and p53(+/-) mice. Our data indicate that RAP80-deficiency promotes genomic instability and causes an increase in cancer risk consistent with the concept that RAP80 exhibits a tumor suppressor function. |
