Cross-Regulation of Protein Stability by p53 and Nuclear Receptor SHP

被引:9
|
作者
Yang, Zhihong [1 ,2 ]
Zhang, Yuxia [1 ,2 ]
Kemper, Jongsook Kim [3 ]
Wang, Li [1 ,2 ]
机构
[1] Univ Utah, Sch Med, Dept Med, Huntsman Canc Inst, Salt Lake City, UT 84112 USA
[2] Univ Utah, Sch Med, Dept Oncol Sci, Huntsman Canc Inst, Salt Lake City, UT USA
[3] Univ Illinois, Dept Mol & Integrat Physiol, Urbana, IL USA
来源
PLOS ONE | 2012年 / 7卷 / 06期
关键词
SMALL HETERODIMER PARTNER; NEGATIVE FEEDBACK-REGULATION; FATTY-ACID SYNTHASE; DIURNAL REGULATION; GENE-EXPRESSION; LIVER RECEPTOR; X RECEPTOR; ERR-GAMMA; INHIBITION; GROWTH;
D O I
10.1371/journal.pone.0039789
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
We report here a novel interplay between tumor suppressor p53 and nuclear receptor SHP that controls p53 and SHP stability. Overexpression of p53 causes rapid SHP protein degradation, which does not require the presence of Mdm2 and is mediated by the proteosome pathway. Overexpressing SHP alone does not affect p53 stability. However, SHP destabilizes p53 by augmentation of Mdm2 ubiquitin ligase activity toward p53. The single amino acid substitution in the SHP protein SHPK170R increases SHP binding to p53 relative to SHP wild-type, whereas SHPG171A variant shows a diminished p53 binding. As a result of the cross-regulation, the tumor suppressor function of p53 and SHP in inhibition of colon cancer growth is compromised. Our findings reveal a unique scenario for a cross-inhibition between two tumor suppressors to keep their expression and function in check.
引用
收藏
页数:8
相关论文
共 50 条
  • [31] Regulation and function of the p53 tumour suppressor protein
    Vousden, K
    BRITISH JOURNAL OF CANCER, 2003, 88 : S7 - S7
  • [32] In vivo analysis of the p53 protein stability network
    Guidry, A.
    Thomas, H.
    Parant, J.
    MOLECULAR BIOLOGY OF THE CELL, 2013, 24
  • [33] Thermal and chemical stability of human p53 protein
    Nichols, NM
    Mrowczynski, E
    Matthews, KS
    BIOPHYSICAL JOURNAL, 2000, 78 (01) : 5A - 5A
  • [34] Stability of p53 oligomers: Tetramerization of p53 impinges on its stability
    Luwang, Johnson Wahengbam
    Nair, Aadithye R.
    Natesh, Ramanathan
    BIOCHIMIE, 2021, 189 : 99 - 107
  • [35] On the cross-regulation of protein tyrosine phosphatases and receptor tyrosine kinases in intracellular signaling
    Haugh, JM
    Schneider, IC
    Lewis, JM
    JOURNAL OF THEORETICAL BIOLOGY, 2004, 230 (01) : 119 - 132
  • [36] Protein stability of p53 targets determines their temporal expression dynamics in response to p53 pulsing
    Hanson, Ryan L.
    Porter, Joshua R.
    Batchelor, Eric
    JOURNAL OF CELL BIOLOGY, 2019, 218 (04): : 1282 - 1297
  • [37] Regulation of p53 and p53 family members.
    Prives, C
    Ahn, J
    DiComo, C
    Gaiddon, C
    Shieh, S
    FASEB JOURNAL, 1999, 13 (07): : A1430 - A1430
  • [38] Metabolic regulation of mutant p53 stability by the mevalonate pathway
    Iwakuma, Tomoo
    Ranjan, Atul
    Iyer, Swathi V.
    Padhye, Subhash
    Weir, Scott
    Roy, Anuradha
    CANCER RESEARCH, 2016, 76
  • [39] Regulation of p53 stability and activity in response to genotoxic stress
    Colman, MS
    Afshari, CA
    Barrett, JC
    MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH, 2000, 462 (2-3) : 179 - 188
  • [40] PTEN and p53 cross-regulation induced by soy isoflavone genistein promotes mammary epithelial cell cycle arrest and lobuloalveolar differentiation
    Rahal, Omar M.
    Simmen, Rosalia C. M.
    CARCINOGENESIS, 2010, 31 (08) : 1491 - 1500