In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 2968-2968
Abstract:
The mitotic checkpoint gene CHFR is silenced by promoter hypermethylation or mutated in various human cancers, suggesting that CHFR is an important tumor suppressor. Recent studies have reported that CHFR functions as an E3 ubiquitin ligase of Aurora A and HDAC1, resulting in the degradation of those proteins. To better understand how CHFR suppresses cell cycle progression and tumorigenesis, we sought to identify CHFR-interacting proteins using affinity purification combined with mass spectrometry. Poly (ADP-ribose) polymerase-1 (PARP-1), which catalyzes polyADP-ribosylation, was newly identified as a CHFR interacting protein. CHFR promoted polyubiquitination of PARP-1. Conversely, PARP-1 poly(ADP-ribosyl)ated CHFR. In addition, we mapped the region of both CHFR and PARP-1 required for the interaction. Because CHFR delays entry into metaphase in response to mitotic stress, we investigated whether PARP-1 is involved in the mitotic checkpoint. In the presence of PARP-1, CHFR arrested the cell cycle. On the other hand, in the absence of PARP-1, CHFR had no effect on the cell cycle arrest. Additionally, we found the knockdown of PARP-1 resulted in cell cycle arrest itself. As overexpression of PARP-1 has been reported in several human tumors, our findings suggest the functional relationships between CHFR and PARP-1 could play an important role in regulation of cell cycle and tumor suppression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2968. doi:10.1158/1538-7445.AM2011-2968
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2011-2968
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2011
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
