Journal article
RGS6 interacts with DMAP1 and DNMT1 and inhibits DMAP1 transcriptional repressor activity
The Journal of biological chemistry, Vol.279(14), pp.14120-14128
04/02/2004
DOI: 10.1074/jbc.M309547200
PMID: 14734556
Abstract
RGS6 is a member of a subfamily of mammalian RGS proteins that possess DEP (disheveled, Egl-10, pleckstrin) and GGL (G protein gamma subunit-like) domains in addition to the hallmark RGS domain. RGS proteins negatively regulate heterotrimeric G protein signaling by virtue of the GTPase-activating protein activity of their RGS domains. RGS6 exists in multiple splice forms with a long (6L) or short (6S) N terminus, a complete or incomplete GGL domain, in combination with various C-terminal domains. Green fluorescent protein-tagged RGS6L and RGS6S forms exhibit predominantly cytoplasmic and nuclear patterns of distribution in COS-7 cells, respectively, and traffic from these sites to nucleoli in response to stress signaling. We undertook a yeast two-hybrid screen for nuclear RGS6-binding proteins and here identify DMAP1 as an RGS6-interacting protein. DMAP1 is a component of the Dnmt1 complex involved in repression of newly replicated genes. The domains of interaction were mapped to the N-terminal region of the GGL domain of RGS6, a region distinct from its Gbeta5 binding region, and the C-terminal domain of DMAP1. Gbeta5 and DMAP1 did not compete for each other's interaction with RGS6. Co-immunoprecipitation studies in COS-7 cells showed that RGS6L and RGS6S, but not RGS6LDelta258-293 deletion mutant lacking a DMAP1-binding module, co-immunoprecipitate DMAP1 as well as Dnmt1 in a DMAP1-dependent manner. A recombinant GGL domain of RGS6 precipitated endogenous DMAP1 and Dnmt1 in neuroblastoma cell lysates and endogenous DMAP1 co-immunoprecipitated with RGS6L from mouse brain. Co-expression of DMAP1 with RGS6L promoted nuclear migration of RGS6L and its co-localization with DMAP1, a response not observed with RGS6LDelta258-293. RGS6 inhibited the transcriptional repressor activity of DMAP1. RGS6 is the first member of the RGS protein family shown to interact with proteins involved in transcriptional regulation.
Details
- Title: Subtitle
- RGS6 interacts with DMAP1 and DNMT1 and inhibits DMAP1 transcriptional repressor activity
- Creators
- Zhengyu Liu - Department of Pharmacology, University of Iowa College of Medicine, Iowa City, Iowa 52242, USARory A Fisher
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.279(14), pp.14120-14128
- DOI
- 10.1074/jbc.M309547200
- PMID
- 14734556
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- United States
- Grant note
- GM-067881 / NIGMS NIH HHS
- Language
- English
- Date published
- 04/02/2004
- Academic Unit
- Iowa Neuroscience Institute; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040305002771
Metrics
15 Record Views