Toggle Main Menu Toggle Search

Open Access padlockePrints

TMF/ARA160 is a BC-box-containing protein that mediates the degradation of Stat3

Lookup NU author(s): Emeritus Professor Elaine Perry

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


Abstract

TMF/ARA160 is a Golgi resident protein whose cellular functions have not been conclusively revealed. Herein we show that TMF/ARA160 can direct the proteasomal degradation of the key cell growth regulator - Stat3. TMF/ARA160 was dispersed in the cytoplasm of myogenic C2C12 cells that were grown under low-serum conditions. The cytoplasmic distribution of TMF/ARA160 was accompanied by its transient association with the tyrosine kinase Fer and with Stat3, which underwent proteasomal degradation under those conditions. Moreover, serum deprivation induced the association of ubiquitinated proteins, with the TMF/ARA160 complex. However, TMF/ARA160 did not bind Stat1, whose cellular levels were increased in serum-starved C2C12 cells. Amino-acid sequence analysis identified a BC-box element in TMF/ARA160 that mediated the binding of this protein to elongin C. Ectopic expression of TMF/ARA160 in serum-starved C2C12 cells drove the ubiquitination and proteasomal degradation of Stat3, an effect that was not caused by TMF/ARA160 devoid of the BC-box motif. Thus, the Golgi apparatus harbors a novel BC-box-containing protein that can direct Stat3 to proteasomal degradation. Interestingly, the level of TMF/ARA160 was significantly decreased in malignant brain tumors, implying a suppressive role of that protein in tumor progression.


Publication metadata

Author(s): Perry E, Tsruya R, Levitsky P, Pomp O, Taller M, Weisberg S, Parris W, Kulkarni S, Malovani H, Pawson T, Shpungin S, Nir U

Publication type: Article

Publication status: Published

Journal: Oncogene

Year: 2004

Volume: 23

Issue: 55

Pages: 8908-19

Print publication date: 25/11/2004

ISSN (print): 0950-9232

ISSN (electronic): 1476-5594

Publisher: Nature Publishing Group

URL: http://www.dx.doi.org/10.1038/sj.onc.1208149

DOI: 10.1038/sj.onc.1208149

Notes: 0950-9232 Journal Article


Altmetrics

Altmetrics provided by Altmetric


Share