Page 5 - N. Metabolism and metabolic diseases

Positive Regulation Of JAK/STAT Signaling With SOCS3 Drived
Cell-Permeable Binding Domain To ObR Induces Anti-Obesity Effect

Kuysook Lee, Jisook Jeon, Sujeong Kim, Hyuntae Kang, Youngsil Choi and Daewoong Jo
Metabolic Disease Team, Cellivery R&D Institute, Cellivery Therapeutics, Inc., Seoul 03929, Korea

BACKGROUND AIM
Leptin, an adipocyte-derived hormone which regulates food intake We hypothesized that an exogenously delivered SOCS3 binding
and energy expenditure, is excessively expressed in obese patients. domain (SH2) would compete with SOCS3 for binding to Tyr985-
Leptin signaling is regulated by a negative feedback regulator, phosphorylated ObR, and thereby maintain leptin-initiated
suppressor of cytokine signaling 3 (SOCS3) that competitively binds JAK/STAT signaling.
to the leptin receptor (ObR) and promotes leptin resistance.

METHODS
Cell-permeable, dominant-interfering ΔSOCS3 protein consists of the SOCS3 SH2 domain (amino acid residues 45-185), a sequence optimized-
advanced macromolecule transduction domain (aMTD) to deliver the protein into cultured cells and animal tissues and a protein solubilization
domain to facilitate large-scale purification of soluble, biologically active proteins. Intracellular delivery of ΔSOCS3 was tested for the ability to
enhance leptin signaling and sensitivity in diet-induced obese (DIO) mice.

RESULTS

CONCLUSION REFERENCES Contact information
CP-ΔSOCS3 appeared to competitively Chung et al. (2020) Science Advances, 6: eaba 1193 Minyong Jung
suppress feedback inhibition of JAK/STAT
signaling by endogenous SOCS3 thereby Lim et al. (2013) Clinical Cancer Research, 19: 680-690 New Drug & Business Development
enhancing leptin sensitivity. This establishes the Lim et al. (2013) Biomaterials, 34: 6261-6271
importance of SOCS3 in the biology of leptin Lim et al. (2012) Molecular Therapy, 20: 1540-1549 Cellivery Therapeutics, Inc.
signaling and resistance and suggests CP- jungmy@cellivery.com
ΔSOCS3 might be used as a mechanism- Jo et al (2005) Nature Medicine, 11: 892-898
specific weight-loss therapy. Jo et al (2001) Nature Biotechnology, 19: 929-933 +82-2-3151-8900