Sumocor is developing small molecule therapeutics that target SUMO1
, a "chaperone" protein that regulates the activity of key transporter genes, which is deficient in the failing heart.
Our previous study demonstrated that high glucose obviously induced the expression of SUMO isoforms (SUMO1, SUMO2/3) in GMCs, subsequently stimulated degradation of I[kappa]B[alpha], and triggered NF-[kappa]B signaling by weakening the interaction between SUMO protein and I[kappa]B[alpha] while promoting ubiquitination of I[kappa]B[alpha] .
In this study, we detected the changes of PIASy, SUMO1, and SUMO2/3; NF-[kappa]B-related signaling molecules (I[kappa]B[alpha], p- I[kappa]B[alpha], p-IKK[gamma], IKK[gamma], NF-[kappa]Bp65, and p-NF-[kappa]Bp65); and downstream proinflammatory cytokines (MCP-1, IL-6) under high-glucose stress when the rGMCs were transfected with PIASy-siRNA or not, aiming to explore the roles of the SUMO E3 ligase PIASy on NF-[kappa]B inflammatory signaling in the pathogenesis of DN.
Consistent with PIASy, the expression of SUMO isoforms (SUMO1 and SUMO2/3) was significantly increased by high glucose in a time- and dose-dependent manner (P < 0.05) (Figure 1(b)).
The results showed that SUMO1 and SUMO2/3 were coimmunoprecipitated with IKK[gamma], and the SUMO-induced modification of IKK[gamma] was detected on endogenously expressed proteins, suggesting that SUMO and IKK[gamma] were able to form a complex in GMCs.
Melchior, "The nucleoporin RanBP2 has SUMO1
E3 ligase activity," Cell, vol.
RHES modifies mHtt through sumoylation, a posttranscriptional process that consists of the addition of the protein SUMO1
(small ubiquitin like modifier) to mutant Htt (mHtt).
Serial Gene name Upregulated (f) Serial Gene number genes/fold number name change (1) Pescadillo (3.2) [up arrow] (8) Ccnf (2) Tfdp-1 (2.2) [up arrow] (9) Cdkn1a (Transcriptional (p21) factor) (3) Rad21 (1.8) [up arrow] (10) Pkd-1 (4) Nfatc1 (1.7) [up arrow] (11) Taf10 (TafII30) (5) Cks1b (1.6) [up arrow] (12) Sfn (6) Ak1 (1.3) [up arrow] (13) Sumo1
(7) Itgb1 (1.2) [up arrow] (14) RAN Serial Downregulated (f) number genes/fold change (1) (0.06) [down arrow] (2) (0.5) [down arrow] (3) (0.5) [down arrow] (4) (0.5) [down arrow] (5) (0.6) [down arrow] (6) (0.7) [down arrow] (7) (0.8) [down arrow]
The team evaluated failing human and pig hearts and discovered that SUMO1, a so-called "chaperone" protein that regulates the activity of key transporter genes, was decreased in failing hearts.
When the researchers injected SUMO1 into these hearts via gene therapy, cardiac function was significantly improved.
This research indicates that SUMO1 may play a critical role in the pathogenesis of heart failure.
"Our experiments over the last four years beginning with the discovery of SUMO1 as an interacting protein of SERCA2a have shown that it plays a critical role in the development of heart failure," said lead researcher Roger J.