Gene interactions and pathways from curated databases and text-mining
Cancer Cell 2010, PMID: 21075311

B55β-associated PP2A complex controls PDK1-directed myc signaling and modulates rapamycin sensitivity in colorectal cancer.

Tan, Jing; Lee, Puay Leng; Li, Zhimei; Jiang, Xia; Lim, Yaw Chyn; Hooi, Shing Chuan; Yu, Qiang

The PP2A serine/threonine protein phosphatase serves as a critical cellular regulator of cell growth, proliferation, and survival. However, how this pathway is altered in human cancer to confer growth advantage is largely unknown. Here, we show that PPP2R2B, encoding the B55β regulatory subunit of the PP2A complex, is epigenetically inactivated by DNA hypermethylation in colorectal cancer. B55β-associated PP2A interacts with PDK1 and modulates its activity toward Myc phosphorylation. On loss of PPP2R2B, mTORC1 inhibitor rapamycin triggers a compensatory Myc phosphorylation in PDK1-dependent, but PI3K and AKT-independent manner, resulting in resistance. Reexpression of PPP2R2B, genetic ablation of PDK1 or pharmacologic inhibition of PDK1 abrogates the rapamycin-induced Myc phosphorylation, leading to rapamycin sensitization. Thus, PP2A-B55β antagonizes PDK1-Myc signaling and modulates rapamycin sensitivity.

Diseases/Pathways annotated by Medline MESH: Cell Transformation, Neoplastic, Colorectal Neoplasms
Document information provided by NCBI PubMed

Text Mining Data

Myc ⊣ mTORC1: " On loss of PPP2R2B, mTORC1 inhibitor rapamycin triggers a compensatory Myc phosphorylation in PDK1 dependent, but PI3K and AKT independent manner, resulting in resistance "

PI3K ⊣ mTORC1: " On loss of PPP2R2B, mTORC1 inhibitor rapamycin triggers a compensatory Myc phosphorylation in PDK1 dependent, but PI3K and AKT independent manner, resulting in resistance "

Manually curated Databases

  • IRef Intact Interaction: Complex of PPP2R1A-RPS6KB1-PPP2R2B (association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: PPP2R1A — PPP2R2B (physical association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: PDPK1 — PPP2R2B (physical association, anti bait coimmunoprecipitation)
  • IRef Intact Interaction: PDPK1 — PPP2R2B (physical association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: PPP2R2B — RPS6KB1 (physical association, anti tag coimmunoprecipitation)
In total, 4 gene pairs are associated to this article in curated databases