Roles of VRK3 in regulation of PARP1 stability and
PARP inhibitor sensitivity
- Title
- Roles of VRK3 in regulation of PARP1 stability and
PARP inhibitor sensitivity
- Authors
- HAN, SEUNG HYUN; KIM, KYONG TAI
- Date Issued
- 2018-11-08
- Publisher
- NCRI
- Abstract
- Poly(ADP-ribose) polymerase 1 (PARP1) is one of the most critical protein in DNA repair response and is highly expressed in breast and ovarian cancer cell. In a cancer therapy, PARP inhibitor, which inhibits its enzyme activity, is considered as a promising drug for BRCA mutated cancer. Recently, as PARP-DNA trapping model was introduced, PARP inhibitors were applied in many other cancer treatments. However, in many cases, it has been reported that tumor has resistance to PARP inhibitor. Emerging evidence indicates that level of PARP1 is critical determinants for PARP inhibitor sensitivity. Many papers show that there is a clear correlation between PARP1 expression and PARP inhibitor sensitivity. Also PARP1 expression is regarded as one of the bio-marker to predict clinical response of many types of cancer. Consequently, identification of regulating mechanism of PARP1 is crucial in overcoming the resistance of PARP inhibitor used for cancer. However, the molecular mechanisms which regulates PARP1 is yet not well known.
Here, we found that VRK3 which is novel protein kinase, is a positive regulator of PARP1 by regulating its protein stability through RNF144a. According to our data, over-expression of VRK3 increases the stability of PARP1 and sensitivity of PARP inhibitor. Inversely, loss of VRK3 results in down-regulation of PARP1. These study indicates that VRK3 has important role in PARP inhibitor sensitivity via regulation of PARP1.
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/97380
- Article Type
- Conference
- Citation
- 2018 NCRI Cancer Conference, 2018-11-08
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