Autophagic Punctum

Direct molecular interactions between HMGB1 and TP53 in colorectal cancer

Volume 8, Issue 5   May 2012
Pages 846 - 848
http://dx.doi.org/10.4161/auto.19891
Keywords: HMGB1, TP53, apoptosis, autophagy, colorectal cancer
Authors: Kristen M. Livesey, Rui Kang, Herbert J. Zeh, III, Michael T. Lotze and Daolin Tang

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Abstract:
Tumorigenesis and the efficacy of cancer therapeutics are both defined by the balance between autophagy and apoptosis. High-mobility group box 1 (HMGB1) is a DNA chaperone and extracellular damage-associated molecular pattern molecule (DAMP) with pro-autophagic activity. TP53/p53 plays a transcription-dependent and -independent role in the regulation of apoptosis, autophagy, metabolism, cell cycle progression, and many other processes. Both HMGB1 and TP53 are tightly linked with the development of cancer, associated with many of the hallmarks defining the altered biology of cancer. We have demonstrated that TP53-HMGB1 complexes regulate the balance between apoptosis and autophagy through regulation of the cytosolic localization of the reciprocal binding partner, whereby increased cytosolic HMGB1 enhances autophagy and increased cytosolic TP53 enhances apoptosis in colon cancer cells. We found that HMGB1-mediated autophagy promotes cell survival in TP53-dependent processes, and that TP53 inhibits autophagy through negative regulation of HMGB1-BECN1 complexes. Nuclear localization of TP53 and HMGB1 in tumors from patients with colon adenocarcinoma had a positive trend with survival time from diagnosis. Thus, HMGB1 and TP53 are critical in the crossregulation of apoptosis and autophagy and central to colon cancer biology.

Autophagic Punctum to:
KM Livesey, R Kang, P Vernon, W Buchser, P Loughran, SC Watkins, et al. p53/HMGB1 Complexes Regulate Autophagy and Apoptosis. Cancer Res 2012; 72: 1996-2005
PMID: 22345153 DOI: 10.1158/0008-5472.CAN-11-2291

Received: February 21, 2012; Accepted: March 2, 2012; Published Online: May 1, 2012

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