The high incidence of childhood adrenocortical cancer in Brazil is linked to a specific mutation in the tumor suppressor p53. As reported in the January 2002 issue of Nature Structural Biology, this mutation affects the stability of the tetrameric p53 in a pH-dependent manner. The finding may provide an explanation for the tissue-specific formation of cancer in young children.
The functional form of the tumor suppressor p53 contains four identical subunits. By using a variety of biophysical techniques, Richard Kriwacki and coworkers at St. Jude Children's Hospital, USA, studied the stability of the p53 domain that is responsible for maintaining the tetrameric organization. They found that when this domain contains a particular mutation (from an arginine to a histidine at position 337), it forms a stable tetramer in a neutral or acidic environment but is unfolded at slightly basic pH values. The authors suggest that the cells in the developing adrenal gland of a child may represent a basic environment, which would destabilize the mutant tetrameric p53; the loss of tumor suppression function in these cells would then lead to cancer formation in the tissue.
Dr. Richard W. Kriwacki
Department of Structural Biology
St. Jude Children's Hospital
Tel: +1 901 495 3290
(C) Nature Structural Biology press release.
Message posted by: Trevor M. D'Souza