Singular v dual inhibition of SNF2L and its isoform, SNF2LT, have similar effects on DNA damage but opposite effects on the DNA damage response, cancer cell growth arrest and apoptosis.

Oncotarget
Yin YeSanford H Barsky

Abstract

SNF2L, an ATPase chromatin remodeling gene nearly ubiquitously expressed in diverse tissues, cancers, and derived cell lines, contributes to the chromatin remodeling complex that facilitates transcription. Because of this near ubiquitous expression, it has not been exploited as a cancer therapeutic target. However, in a recent study, we found that highly malignant cancer cells, although expressing SNF2L at similar levels as their normal counterparts, were sensitive to its knockdown. Only the highly malignant (HM) lines showed significant growth inhibition, DNA damage, a DNA damage response, and phosphorylation of checkpoint proteins and marked apoptosis. In studying SNF2L, we discovered a novel truncated isoform, SNF2LT which, when compared to full length SNF2L, lacked three important domains: HAND, SANT and SLIDE. Although truncated isoforms usually have antagonistic functions to their parental molecule, here SNF2LT knockdown had similar effects to the knockdown of its parental molecule, SNF2L, of inducing DNA damage, a DNA damage response, cell cycle arrest and apoptosis selectively in cancer cell lines. However dual SNF2L and SNF2LT knockdown, while inducing DNA damage, did not result in a DNA damage response, a cell cycle a...Continue Reading

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Datasets Mentioned

BETA
EU36009

Methods Mentioned

BETA
Antibody
Transfection
electrophoresis
PCR
Protein Assay
xenograft
transfections

Software Mentioned

7500 System SDS

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