Mediates CD8 T Cell Death via Regulation of Bcl2-Mediated Restriction of outer Mitochondrial Membrane Integrity.

The SET and domain 1 () locus encodes three tissue-restricted isoforms. Two previously characterized isoforms, and are heart and skeletal muscle-restricted histone methyl transferases. Here we report that a third, non-catalytic isoform, is expressed predominantly in activated CD8 T cells.

The L2a element is a mouse CD8 silencer that interacts with MAR-binding proteins SATB1 and CDP.

Previous transgenic-reporter and targeted-deletion studies indicate that the subset-specific expression of CD8αβ heterodimers is controlled by multiple enhancer activities, since no silencer elements had been found within the locus. We have identified such a silencer as L2a, a previously characterized ∼ 220 bp nuclear matrix associating region (MAR) located ∼ 4.5 kb upstream of CD8α.

Determination of substrate motifs for human Chk1 and hCds1/Chk2 by the oriented peptide library approach.

Mammalian Chk1 and Chk2 are two Ser/Thr effector kinases that play critical roles in DNA damage-activated cell cycle checkpoint signaling pathways downstream of ataxia telangiectasia-mutated and ataxia telangiectasia-related. Endogenous substrates have been identified for human hCds1/Chk2 and Chk1; however, the sequences surrounding the substrate residues appear unrelated, and consensus substrate motifs for the two Ser/Thr kinases remain unknown. We have utilized peptide library analyses to develop specific, highly preferred substrate motifs for hCds1/Chk2 and Chk1.

The scid defect affects the final step of the immunoglobulin VDJ recombinase mechanism.

Abelson murine leukemia virus-transformed precursor B lymphocytes from scid (severe combined immunodeficient) mice, like A-MuLV transformants from normal mice, actively rearrange segments of their Ig heavy chain variable region gene locus during growth in culture. Targeting of recombination to appropriate segments appears normal in these lines as evidenced by initial rearrangement of sequences from within the D and JH locus to form aberrant "DJH" rearrangements and secondary rearrangement of sequences from within the VH locus to the aberrant "DJH" intermediates. A detailed analysis of the joints in these rearrangements indicates that the VDJ recombinase in scid pre-B cells can correctly recognize heptamernonamer signal sequences and perform precise endonucleolytic scissions at these sequences.