Polypeptides of the lens fibre cell intracellular matrix

Summary The cytoskeletal proteins of the vertebrate lens fibre cell comprise polypeptides ranging in mol.wt from 43,000 to 250,000 daltons. The main intermediate filament polypeptide of the pickerel, Northern frog, chick, bovine, and human lens has a mol.wt of 54,000 daltons. Peptide analysis revealed that the chick 54,000 dalton protein was more similar to the bovine protein than to the pickerel protein.Supported by grants EY 01417 (H. Maisel) and HD-06390 (J.C. Brown, University of Virginia, Charlottesville) from the National Institutes of Health, U.S.P.H.S.     

A continuum model for tumour suppression

This year, 2011, marks the forty-year anniversary of the statistical analysis of retinoblastoma that provided the first evidence that tumorigenesis can be initiated by as few as two mutations. This work provided the foundation for the two-hit hypothesis that explained the role of recessive tumour suppressor genes (TSGs) in dominantly inherited cancer susceptibility syndromes. However, four decades later, it is now known that even partial inactivation of tumour suppressors can critically contribute to tumorigenesis. Here we analyse this evidence and propose a continuum model of TSG function to explain the full range of TSG mutations found in cancer.     

Missense glucokinase mutation in maturity-onset diabetes of the young and mutation screening in late-onset diabetes.

We describe a codon 299 mutation in the glucokinase gene in a British pedigree with maturity-onset diabetes of the young (MODY) resulting in a substitution of glycine to arginine. One out of fifty patients diagnosed with classical late-onset type 2 diabetes mellitus was also found to have this mutation. All nine relatives of this patient who have inherited the mutation have type 2 diabetes, although six others without the mutation are also present with diabetes. The discovery that glucokinase mutations can cause MODY and was also found in ten affected members of a pedigree with type 2 diabetes in which MODY had not previously been considered indicates that diagnosis based on molecular pathology will be helpful in understanding the aetiology of type 2 diabetes.