Comparative proteomic analysis reveals a function of the novel death receptor-associated protein BRE in the regulation of prohibitin and p53 expression and proliferation.
The brain and reproductive organ expressed (BRE) gene encodes a highly conserved stress-modulating protein. To gain further insight into the function of this gene, we used comparative proteomics to investigate the protein profiles of C2C12 and D122 cells resulting from small interfering RNA (siRNA)-mediated silencing as well as overexpression of BRE. Silencing of BRE in C2C12 cells, using siRNA, resulted in up-regulated Akt-3 and carbonic anhydrase III expression, while the 26S proteasome regulatory subunit S14 and prohibitin were down-regulated. Prohibitin is a potential tumour suppressor gene, which can directly interact with p53. We found that cell proliferation was significantly increased after knockdown of BRE, concomitant with reduced p53 and prohibitin expression. In contrast, we observed decreased proliferation and up-regulation of p53 and prohibitin when BRE was overexpressed in the D122 cell line. In total, five proteins were found to be up-regulated after BRE over-expression. The majority of these proteins can target or crosstalk with NF-kappaB, which plays a central role in regulating cell proliferation, differentiation and survival. Our results establish a crucial role for BRE in the regulation of key proteins of the cellular stress-response machinery and provide an explanation for the multifunctional nature of BRE.
Tang
Mei Kuen
MK
Department of Anatomy, Basic Medical Science Building, Chinese University of Hong Kong, Shatin, Hong Kong, PR China.
Wang
Chun Mei
CM
Shan
Sze Wan
SW
Chui
Yiu Loon
YL
Ching
Arthur Kar Keung
AK
Chow
Pak Ham
PH
Grotewold
Lars
L
Chan
John Yeuk Hon
JY
Lee
Kenneth Ka Ho
KK
D000818:Animals; D024403:Carbonic Anhydrase III / Q000096:biosynthesis; D002460:Cell Line; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000502:physiology*; D000091402:Prohibitins; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis; D034741:RNA, Small Interfering / Q000378:metabolism; D012097:Repressor Proteins / Q000096:biosynthesis*; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry*
C091514:BABAM2 protein, human; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D000091402:Prohibitins; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53; D051057:Proto-Oncogene Proteins c-akt; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; D024403:Carbonic Anhydrase III