title: Ubiquitin specific protease 2 acts as a key modulator for the regulation of cell cycle by adiponectin and leptin in cancer cells.
abstract: Adiponectin and leptin, both produced from adipose tissue, cause cell cycle arrest and progression, respectively in cancer cells. Ubiquitin specific protease-2 (USP-2), a deubiquitinating enzyme, is known to impair proteasome-induced degradation of cyclin D1, a critical cell cycle regulator. Herein, we investigated the effects of these adipokines on USP-2 expression and its potential role in the modulation of cell cycle. Treatment with globular adiponectin (gAcrp) decreased, whereas leptin increased USP-2 expression both in human hepatoma and breast cancer cells. In addition, overexpression or gene silencing of USP-2 affected cyclin D1 expression and cell cycle progression/arrest by adipokines. Adiponectin and leptin also modulated in vitro proteasomal activity, which was partially dependent on USP-2 expression. Taken together, our results reveal that modulation of USP-2 expression plays a crucial role in cell cycle regulation by adipokines. Thus, USP-2 would be a promising therapeutic target for the modulation of cancer cell growth by adipokines.
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsangbuk-do 712-749, Republic of Korea.
authors.forename: Saroj
authors.initials: S
authors.lastname: Nepal
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsangbuk-do 712-749, Republic of Korea.
authors.forename: Anup
authors.initials: A
authors.lastname: Shrestha
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsangbuk-do 712-749, Republic of Korea. Electronic address: parkp@yu.ac.kr.
authors.forename: Pil-Hoon
authors.initials: PH
authors.lastname: Park
mesh_terms: D052242:Adiponectin / Q000502:physiology*; D059447:Cell Cycle Checkpoints; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D010450:Endopeptidases / Q000502:physiology*; D015870:Gene Expression; D056945:Hep G2 Cells; D006801:Humans; D020738:Leptin / Q000502:physiology*; D061986:MCF-7 Cells; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D043222:Ubiquitin Thiolesterase; D015854:Up-Regulation
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; C530104:CCND1 protein, human; D020738:Leptin; D019938:Cyclin D1; D010450:Endopeptidases; C108665:USP2 protein, human; D043222:Ubiquitin Thiolesterase; D046988:Proteasome Endopeptidase Complex
keywords: Adiponectin; Cell cycle; Cyclin D1; Leptin; USP-2