Journal article
RGS6 Sensitizes MCF‐7 Cells To Doxorubicin‐induced p53 Phosphorylation
The FASEB journal, Vol.20(5), pp.A912-A912
03/2006
DOI: 10.1096/fasebj.20.5.A912-a
Abstract
RGS6 is a member of the RGS protein family of heterotimeric G protein regulators and exists in thirty‐six splice variant forms. As a member of the RGS family, RGS6 is proposed to function as a regulator of G protein signaling by acting as a GTPase‐activating protein for certain G[alpha] subunits. Yet, several observations suggest that RGS6 may have functions distinct from its ability to interact with G proteins. A polymorphism in the human RGS6 gene is associated with reduced risk of bladder cancer, suggesting a possible role of RGS6 in modulating abnormal cell proliferation. Here, we examined whether RGS6 sensitizes cells to DNA damage‐induced responses. Expression of RGS6L in COS‐7 cells promoted micronuclei formation and dramatically sensitized cells to doxorubicin‐induced nuclear abnormalities. We then examined the influence of RGS6 on DNA damage signaling responses to a low dose of doxorubicin (0.7[micro]M) in MCF‐7 cells infected with RGS6L‐EGFP or EGFP adenovirus. Doxorubicin produced dramatic increases in both Ser15 p53 and Thr68 Chk2 phosphorylation in RGS6L transfectants but produced increases only in Chk2 phosphorylation in EGFP transfectants. DNA damage‐induced activation of ATM and resulting phosphorylation of Chk2 and p53 promote cell cycle arrest and apoptosis. The finding that doxorubicin promoted increases in p53 phosphorylation only in RGS6‐expressing cells demonstrates selective modulation of DNA damage signaling responses by RGS6. These results provide the first evidence that RGS6 may have a novel function in modulating DNA damage responses by selectively enhancing p53 phosphorylation. (NIH GM067881)
Details
- Title: Subtitle
- RGS6 Sensitizes MCF‐7 Cells To Doxorubicin‐induced p53 Phosphorylation
- Creators
- Daisuke Mayuzumi - University of Iowa Carver College of MedicineTapan K Chatterjee - University of Iowa Carver College of MedicineRory A Fisher - University of Iowa Carver College of Medicine
- Resource Type
- Journal article
- Publication Details
- The FASEB journal, Vol.20(5), pp.A912-A912
- Publisher
- Federation of American Societies for Experimental Biology
- DOI
- 10.1096/fasebj.20.5.A912-a
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Number of pages
- 1
- Language
- English
- Date published
- 03/2006
- Academic Unit
- Iowa Neuroscience Institute; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984071735502771
Metrics
6 Record Views