Molecular Medicine

, Volume 20, Issue 1, pp 359–362 | Cite as

High Mobility Group Box 1 (HMGB1) Phenotypic Role Revealed with Stress

  • Daolin Tang
  • Rui Kang
  • Bennett Van Houten
  • Herbert J. Zeh
  • Timothy R. Billiar
  • Michael T. Lotze


High mobility group box 1 (HMGB1) is an evolutionarily ancient protein that is present in one form or another in all eukaryotes. It fundamentally resides in the nucleus but translocates to the cytosol with stress and is subsequently released into the extracellular space. HMGB1 global knockout mice exhibit lethal hypoglycemia, whereas tissues and cells from conditional knockout or knock-in mice are born alive without apparent significant functional deficit. An aberrant response to targeted stress in the liver, pancreas, heart or myeloid cells is consistent with a protective role for HMGB1 in sustaining nuclear homeostasis and enabling other stress responses, including autophagy. Under some conditions, HMGB1 is not required for liver and heart function. Many challenges remain with respect to understanding the multiple roles of HMGB1 in health and disease.



The authors thank Christine Heiner (Department of Surgery, University of Pittsburgh) for her critical reading of the manuscript. This work was supported by the National Institutes of Health (grant R01CA160417 to D Tang and grant R01 CA181450 to HJ Zeh and MT Lotze) and a 2013 Pancreatic Cancer Action Network-AACR Career Development Award (grant 13-20-25-TANG).


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Authors and Affiliations

  • Daolin Tang
    • 1
  • Rui Kang
    • 1
  • Bennett Van Houten
    • 2
    • 3
  • Herbert J. Zeh
    • 1
  • Timothy R. Billiar
    • 1
  • Michael T. Lotze
    • 1
  1. 1.Department of SurgeryUniversity of PittsburghPittsburghUSA
  2. 2.Department of PharmacologyUniversity of PittsburghPittsburghUSA
  3. 3.Department of Chemical BiologyUniversity of PittsburghPittsburghUSA

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