SHARPIN Lentiviral Activation Particles (h): sc-404836-LAC

SHARPIN (SHANK-associated RH domain interactor) is a core component of the linear ubiquitin chain assembly complex (LUBAC), where it cooperates with RNF31/HOIP and RBCK1/HOIL-1L to regulate Met1-linked ubiquitination and downstream NF-κB signaling. Through control of ubiquitin-dependent signaling at receptors such as TNFR and pattern-recognition pathways, SHARPIN helps tune inflammatory responses, cell survival programs, and proteostasis. SHARPIN has also been implicated in modulation of PTEN/PI3K–AKT signaling and cytoskeletal or adhesion-associated processes, connecting it to proliferation, migration, and stress-response phenotypes. Dysregulated SHARPIN activity is therefore studied in contexts including chronic inflammation, immune signaling defects, and cancer-associated pathway rewiring.

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

SHARPIN Lentiviral Activation Particles (h) 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 SHARPIN transcriptional start site, where VP64, p65, and HSF1 act cooperatively to recruit endogenous transcriptional machinery and drive sustained upregulation of endogenous SHARPIN expression. The use of nuclease-inactive dCas9 avoids the introduction of double-strand DNA breaks and preserves the native SHARPIN 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.