ATF-6α Lentiviral Activation Particles (m): sc-432646-LAC

Activating transcription factor 6 (ATF-6α) is an ER-resident transmembrane sensor that is cleaved and translocated to the nucleus during endoplasmic reticulum stress, where it induces transcriptional programs that restore proteostasis. As a central branch of the unfolded protein response, ATF-6α coordinates ER chaperone expression, ER-associated degradation components, and secretory pathway remodeling, integrating with PERK and IRE1 signaling to regulate cell survival and adaptation. In mouse systems, Atf6 modulation is used to study secretory cell function, oxidative and metabolic stress handling, and inflammatory signaling crosstalk. Dysregulated ATF6 signaling has been linked to proteostasis imbalance observed in models of neurodegeneration, diabetes-related stress, and cardiac remodeling, making it a relevant node for mechanistic pathway analysis.

ATF-6α Lentiviral Activation Particles (m) address this need by packaging the complete synergistic activation mediator (SAM) transcriptional activation system into transduction-ready, high-titer lentiviral particles, enabling efficient Atf6 upregulation across a broader range of human cell types.

ATF-6α Lentiviral Activation Particles (m) deliver all functional components of the synergistic activation mediator (SAM) system via lentiviral transduction. The system comprises three particle preparations co-transduced into target cells: one encoding catalytically inactive dCas9 (D10A and N863A mutations) fused to the VP64 transactivation domain with a blasticidin resistance gene; one encoding the MS2-p65-HSF1 fusion protein with a hygromycin resistance gene; and one encoding a target-specific 20 nt sgRNA fused to two MS2 RNA aptamers with a puromycin resistance gene. Following lentiviral transduction and genomic integration of the expression cassettes, the SAM components are stably expressed and assemble at the target locus within the proximal promoter region upstream of the Atf6 transcriptional start site, where VP64, p65, and HSF1 act cooperatively to recruit endogenous transcriptional machinery and drive sustained upregulation of endogenous ATF-6α expression. The use of nuclease-inactive dCas9 avoids the introduction of double-strand DNA breaks and preserves the native Atf6 genomic locus and regulatory architecture.

The lentiviral format offers several practical advantages: stable genomic integration supports heritable activation across cell divisions; high-titer particle preparations eliminate the need for in-house viral production; and compatibility with primary, non-dividing, and transfection-resistant cell types expands experimental accessibility. Successful transduction can be confirmed and enriched through triple antibiotic selection using puromycin, hygromycin, and blasticidin.

For Research Use Only. Not Intended for Diagnostic or Therapeutic Use.