Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Two alleles of NF-kappaB in the sea anemone Nematostella vectensis are widely dispersed in nature and encode proteins with distinct activities.

PloS one | Oct 6, 2009

BACKGROUND: NF-kappaB is an evolutionarily conserved transcription factor that controls the expression of genes involved in many key organismal processes, including innate immunity, development, and stress responses. NF-kappaB proteins contain a highly conserved DNA-binding/dimerization domain called the Rel homology domain. METHODS/PRINCIPAL FINDINGS: We characterized two NF-kappaB alleles in the sea anemone Nematostella vectensis that differ at nineteen single-nucleotide polymorphisms (SNPs). Ten of these SNPs result in amino acid substitutions, including six within the Rel homology domain. Both alleles are found in natural populations of Nematostella. The relative abundance of the two NF-kappaB alleles differs between populations, and departures from Hardy-Weinberg equilibrium within populations indicate that the locus may be under selection. The proteins encoded by the two Nv-NF-kappaB alleles have different molecular properties, in part due to a Cys/Ser polymorphism at residue 67, which resides within the DNA recognition loop. In nearly all previously characterized NF-kappaB proteins, the analogous residue is fixed for Cys, and conversion of human RHD proteins from Cys to Ser at this site has been shown to increase DNA-binding ability and increase resistance to inhibition by thiol-reactive compounds. However, the naturally-occurring Nematostella variant with Cys at position 67 binds DNA with a higher affinity than the Ser variant. On the other hand, the Ser variant activates transcription in reporter gene assays more effectively, and it is more resistant to inhibition by a thiol-reactive compound. Reciprocal Cys<->Ser mutations at residue 67 of the native Nv-NF-kappaB proteins affect DNA binding as in human NF-kappaB proteins, e.g., a Cys->Ser mutation increases DNA binding of the native Cys variant. CONCLUSIONS/SIGNIFICANCE: These results are the first demonstration of a naturally occurring and functionally significant polymorphism in NF-kappaB in any species. The functional differences between these alleles and their uneven distribution in the wild suggest that different genotypes could be favored in different environments, perhaps environments that vary in their levels of peroxides or thiol-reactive compounds.

Pubmed ID: 19806194 RIS Download

Mesh terms: Alleles | Animals | Cysteine | DNA | Dimerization | Haplotypes | Models, Genetic | NF-kappa B | Phylogeny | Polymorphism, Genetic | Protein Binding | Protein Structure, Tertiary | Sea Anemones | Serine | Transcription Factor RelA

Research resources used in this publication

None found

Research tools detected in this publication

Data used in this publication

None found

Associated grants

  • Agency: NIEHS NIH HHS, Id: P42 ES007381
  • Agency: NCI NIH HHS, Id: R01 CA047763
  • Agency: NIEHS NIH HHS, Id: 5 P42 ES07381
  • Agency: NCI NIH HHS, Id: CA047763

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.


EPA

http://www.epa.gov/epahome/grants.htm

tool

View all literature mentions

National Institutes of Health

NIH is the nations medical research agency - making important medical discoveries that improve health and save lives. The National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services, is the primary Federal agency for conducting and supporting medical research. Helping to lead the way toward important medical discoveries that improve peoples health and save lives, NIH scientists investigate ways to prevent disease as well as the causes, treatments, and even cures for common and rare diseases. NIH research impacts: * child and teen health, * men's health, * minority health, * seniors' health, * women's health, and * wellness and lifestyle issues. Composed of 27 Institutes and Centers, the NIH provides leadership and financial support to researchers in every state and throughout the world.

tool

View all literature mentions

National Science Foundation

An independent federal agency created by Congress to promote the progress of science; to advance the national health, prosperity, and welfare; to secure the national defense They are the funding source for approximately 20 percent of all federally supported basic research conducted by America''s colleges and universities. In many fields such as mathematics, computer science and the social sciences, NSF is the major source of federal backing. NSF leadership has two major components: a director who oversees NSF staff and management responsible for program creation and administration, merit review, planning, budget and day-to-day operations; and a 24-member National Science Board (NSB) of eminent individuals that meets six times a year to establish the overall policies of the foundation.The director and all Board members serve six year terms. Each of them, as well as the NSF deputy director, is appointed by the President of the United States and confirmed by the U.S. Senate. At present, NSF has a total workforce of about 2,100 at its Arlington, Va., headquarters, including approximately 1,400 career employees, 200 scientists from research institutions on temporary duty, 450 contract workers and the staff of the NSB office and the Office of the Inspector General. NSF is the only federal agency whose mission includes support for all fields of fundamental science and engineering, except for medical sciences. They are tasked with keeping the United States at the leading edge of discovery in areas from astronomy to geology to zoology. So, in addition to funding research in the traditional academic areas, the agency also supports high-risk, high pay-off ideas, novel collaborations and numerous projects that may seem like science fiction today, but which the public will take for granted tomorrow. And in every case, they ensure that research is fully integrated with education so that today''s revolutionary work will also be training tomorrow''s top scientists and engineers NSF''s task of identifying and funding work at the frontiers of science and engineering is not a top-down process.

tool

View all literature mentions