Subunits of mammalian SWI/SNF (mSWI/SNF or BAF) complexes have recently been implicated as tumor suppressors in human malignancies. To understand the full extent of their involvement, we conducted a proteomic analysis of endogenous mSWI/SNF complexes, which identified several new dedicated, stable subunits not found in yeast SWI/SNF complexes, including BCL7A, BCL7B and BCL7C, BCL11A and BCL11B, BRD9 and SS18. Incorporating these new members, we determined mSWI/SNF subunit mutation frequency in exome and whole-genome sequencing studies of primary human tumors. Notably, mSWI/SNF subunits are mutated in 19.6% of all human tumors reported in 44 studies. Our analysis suggests that specific subunits protect against cancer in specific tissues. In addition, mutations affecting more than one subunit, defined here as compound heterozygosity, are prevalent in certain cancers. Our studies demonstrate that mSWI/SNF is the most frequently mutated chromatin-regulatory complex (CRC) in human cancer, exhibiting a broad mutation pattern, similar to that of TP53. Thus, proper functioning of polymorphic BAF complexes may constitute a major mechanism of tumor suppression.

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Proteomic and bioinformatic analysis of mammalian SWI/SNF complexes identifies extensive roles in human malignancy

Publisher Summary This chapter describes several techniques for the isolation of Escherichia coli ribosomes, and various methods for the dissociation of ribosomal subunits into their macromolecular constituents and for the reconstitution of ribosomal particles from these constituents. The partial reconstitution is based upon the discovery that isolated ribosomal subunits subjected to CsCI density-gradient equilibrium centrifugation lose a distinct fraction of their original protein. The 50 S ribosomes are converted into 40 S core particles and split proteins (SP50); 30 S ribosomes into 23 S core particles and split proteins (SP30). For the reconstitution of 30 S ribosomal subunits, the presence of phosphate is not essential. The biological activity of reconstituted ribosomal particles and of native ribosomes is generally assayed in a poly (U)-dependent phenylalanine incorporation system.

[41] Reconstitution of ribosomes from subribosomal components

Ribosomal proteins. Protein compositions of biosynthetic precursors and artifical subparticles from ribosomal subunits in Escherichia coli K 12.

Characterization and preliminary attempts for derivatization of crystals of large ribosomal subunits from Haloarcula marismortui diffracting to 3 A resolution.

Abraham Atsmon

Papers

Detachment of ribosomal proteins by salt. I. Effect of conditions on the amount of protein detached.

Detachment of ribosomal proteins by salt: II. Some properties of protein-deficient particles formed by the detachment of ribosomal proteins☆

Characterization of the particulate and free proteins obtained after treatment of ribosomes with 2 M-lithium chloride.