Rabbit Anti-Human RELA (Acetyl-Lys218) polyclonal antibody

Protein-dominant cellular processes cannot be fully decoded without precise manipulation of their activity and localization in living cells. Advances in optogenetics have allowed spatio-temporal control over cellular proteins with molecular specificity; however, these methods require recombinant expression of fusion proteins, possibly leading to conflicting results. Instead of modifying proteins of interest, in this work, we focus on design of a tunable recognition unit and develop an aptamer-based near-infrared (NIR) light-responsive nano-platform for manipulating the subcellular localization of specific proteins in their native states. Our results demonstrate that this nanoplatform allows photocontrol over the cytoplasmicnuclear shuttling behavior of the target RelA protein (a member of the NF-kappa beta family), enabling regulation of RelA-related signaling pathways. With a modular design, this aptamer-based nanoplatform can be readily extended for the manipulation of different proteins (e.g., lyso-zyme and p53), holding great potential to develop a variety of label-free protein photoregulation strategies for studying complex biological events.

Human T-cell leukemia viruses type 1 (HTLV-1) and type 2 (HTLV-2) share a common genome organization and expression strategy but have distinct pathological properties. HTLV-1 is the etiological agent of Adult T-cell Leukemia (ATL) and of HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP), whereas HTLV-2 does not cause hematological disorders and is only sporadically associated with cases of subacute myelopathy. Both HTLV genomes encode two regulatory proteins that play a pivotal role in pathogenesis: the transactivating Tax-1 and Tax-2 proteins and the antisense proteins HBZ and APH-2, respectively. We recently reported that Tax-1 and Tax-2 form complexes with the TNF-receptor associated factor 3, TRAF3, a negative regulator of the non-canonical NF-kappa B pathway. The NF-kappa B pathway is constitutively activated by the Tax proteins, whereas it is inhibited by HBZ and APH-2. The antagonistic effects of Tax and antisense proteins on NF-kappa B activation have not yet been fully clarified. Here, we investigated the effect of TRAF3 interaction with HTLV regulatory proteins and in particular its consequence on the subcellular distribution of the effector p65/RelA protein. We demonstrated that Tax-1 and Tax-2 efficiency on NF-kappa B activation is impaired in TRAF3 deficient cells obtained by CRISPR/Cas9 editing. We also found that APH-2 is more effective than HBZ in preventing Tax-dependent NF-kappa B activation. We further observed that TRAF3 co-localizes with Tax-2 and APH-2 in cytoplasmic complexes together with NF-kappa B essential modulator NEMO and TAB2, differently from HBZ and TRAF3. These results contribute to untangle the mechanism of NF-kappa B inhibition by HBZ and APH-2, highlighting the different role of the HTLV-1 and HTLV-2 regulatory proteins in the NF-kappa B activation.