Molecular basis of heavy-chain class switching and switch region deletion in an Abelson virus-transformed cell line

We demonstrated that a subclone of an Abelson murine leukemia virus-transformed B-lymphoid cell line switched from mu to gamma 2b expression in vitro, by the classical recombination-deletion mechanism. In this line, the expressed VHDJH region and the C gamma 2b constant region gene were juxtaposed by a recombination event which linked the highly repetitive portions of the S mu and S gama 2b regions and resulted in the loss of the C mu gene from the intervening region. An additional recombination event in this subclone involved an internal deletion in the S mu region of the expressed (switched) allele. One end of this deletion occurred very close to the switch recombination point. Despite the recombination-deletion mechanism of switching, the gamma 2b-producing line retained two copies of the C mu gene and two copies of the sequence just 5' to the S gamma 2b recombination point. The possible significance of the retention of these sequences to the mechanism of class switching is discussed

Development of Rational Drug Combinations with Investigational Targeted Agents

This manuscript explores specific examples and criteria in which an alternative regulatory process to the existing combination rule would be appropriate and feasible and thus could be adopted by developers

A single nucleotide polymorphism in the MDM2 promoter attenuates the p53 tumor suppressor pathway and accelerates tumor formation in humans

The tumor suppressor protein, p53, is activated upon cellular stresses such as DNA damage and oncogene activation and initiates a transcriptional program which leads to DNA repair, cell cycle arrest, and in some cases