PMA induces SnoN proteolysis and CD61 expression through an autocrine mechanism

Chonghua Li, Natoya Peart, Zhenyu Xuan, Dorothy E. Lewis, Yang Xia, Jianping Jin

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Phorbol-12-myristate-13-acetate, also called PMA, is a small molecule that activates protein kinase C and functions to differentiate hematologic lineage cells. However, the mechanism of PMA-induced cellular differentiation is not fully understood. We found that PMA triggers global enhancement of protein ubiquitination in K562, a myelogenous leukemia cell line and one of the enhanced-ubiquitination targets is SnoN, an inhibitor of the Smad signaling pathway. Our data indicated that PMA stimulated the production of Activin A, a cytokine of the TGF-β family. Activin A then activated the phosphorylation of both Smad2 and Smad3. In consequence, SnoN is ubiquitinated by the APCCdh1 ubiquitin ligase with the help of phosphorylated Smad2. Furthermore, we found that SnoN proteolysis is important for the expression of CD61, a marker of megakaryocyte. These results indicate that protein ubiquitination promotes megakaryopoiesis via degrading SnoN, an inhibitor of CD61 expression, strengths the roles of ubiquitination in cellular differentiation.

Original languageEnglish (US)
Pages (from-to)1369-1378
Number of pages10
JournalCellular Signalling
Volume26
Issue number7
DOIs
StatePublished - Jul 2014

Keywords

  • Activin A
  • Cdh1
  • Differentiation
  • Smad2
  • SnoN
  • Ubiquitin

ASJC Scopus subject areas

  • Cell Biology

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