HMGB1 regulates autophagy through increasing transcriptional activities of JNK and ERK in human myeloid leukemia cells

Mingyi Zhao, Minghua Yang, Liangchun Yang, Yan Yu, Min Xie, Shan Zhu, Rui Kang, Daolin Tang, Zhigang Jiang, Wuzhou Yuan, Xiushan Wu, Lizhi Cao

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

HMGB1 is associated with human cancers and is an activator of autophagy which mediates chemotherapy resistance. We here show that the mRNA levels of HMGB1 are high in leukemia cells and it is involved in the progression of childhood chronic myeloid leukemia (CML). HMGB1 decreases the sensitivity of human myeloid leukemia cells K562 to anti-cancer drug induced death through up-regulating the autophagy pathway, which is confirmed by the observation with an increase in fusion of autophagosomes and autophagolysosomes. When overexpressing HMGB1, both mRNA levels of Beclin-1, VSP34 and UVRAG which are key genes involved in mammalian autophagy and protein levels of p-Bcl-2 and LC3-II are increased. Luciferase assays document that over-expression of HMGB1 increases the transcriptional activity of JNK and ERK, which may be silenced by siRNA. The results suggest that HMGB1 regulates JNK and ERK required for autophagy, which provides a potential drug target for therapeutic interventions in childhood CML.

Original languageEnglish (US)
Pages (from-to)601-606
Number of pages6
JournalBMB Reports
Volume44
Issue number9
DOIs
StatePublished - Sep 2011
Externally publishedYes

Keywords

  • Autophagy
  • Beclin-1
  • Erk
  • Hmgb1
  • Jnk
  • Myeloid leukemia cell
  • Uvrag
  • Vps34

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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