An ubiquitin-specific peptidase that potentially promote cancer cell necrosis

"ubiquitin-specific peptidase 21 (USP21) has been identified as another essential player in regulation of tumor necrosis factor alpha (TNF-alpha)-induced nuclear factor kappaB (NF-kappaB) activation by working on receptor-interacting protein 1(RIP1)." Scientists in Baylor College of Medicine reported recently in the issue of the Journal of Biological Chemistry, 2010; 285(2):969-78. Dr. Jianhua Yang, Assistant Professor in Pediatrics at Baylor College of Medicine and Texas Children's Cancer Center was the senior author of this research.

"Using a combination of functional genomic and proteomic approaches, we have identified ubiquitin-specific peptidase 21 (USP21) as a deubiquitinase for RIP1," Wrote Dr. Gufeng Xu, researcher in department of pediatrics in Baylor College of Medicine and Texas Children's Cancer Center, and first author of the study appearing in the issue of the Journal of Biological Chemistry. Dr. Xu and his colleagues updated data as "USP21 is constitutively associated with RIP1 and deubiquitinates RIP1 in vitro and in vivo." Dr. Xu wrote: "Notably, knockdown of USP21 in HeLa cells enhances TNF-alpha-induced RIP1 ubiquitination, IkappaB kinase beta (IKKbeta), and NF-kappaB phosphorylation." and the down-stream effects involved the inhibition of NF-kappaB alpha (IkappaB alpha) phosphorylation and ubiquitination, as well as NF-kappaB-dependent gene expression as well".

The researchers concluded at the end of the paper: "Therefore, our results demonstrate that USP21 plays an important role in the down-regulation of TNF-alpha-induced NF-kappaB activation through deubiquitinating RIP1."

Dr. Xu continued: "To the best of our knowledge, this is the first study that links USP21 to human cancer regulator receptor-interacting protein 1 and substantiates what we would've expected of RIP1-USP21 constitutively association, and USP21 is yet another essential player in the almost most important and complicated cancer necrosis process regulation." "These results suggested that USP21 restrain the anti-tumor potential of an invasive cancer cell line."

Journal Reference:
Gufeng Xu, Xiaojie Tan, Hongmei Wang, Wenjing Sun, Yi Shi, Susan Burlingame, Xue Gu, Guangwen Cao, Ting Zhang, Jun Qin and Jianhua Yang. Ubiquitin-specific Peptidase 21 Inhibits Tumor Necrosis Factor α-induced Nuclear Factor κB Activation via Binding to and Deubiquitinating Receptor-interacting Protein 1 J Biol Chem. 2010; 8; 285(2):969-78. DOI: 10.1074/jbc.M109.042689