Αρχειοθήκη ιστολογίου

Αλέξανδρος Γ. Σφακιανάκης
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5
Άγιος Νικόλαος Κρήτη 72100
2841026182
6032607174

Κυριακή 17 Φεβρουαρίου 2019

Heat shock protein 27 inhibits HMGB1 translocation by regulating CBP acetyltransferase activity and ubiquitination

Publication date: April 2019

Source: Molecular Immunology, Volume 108

Author(s): Xiaowen Bi, Miao Xu, Jinfei Li, Ting Huang, Baolin Jiang, Lei Shen, Lan Luo, Shixiang Liu, Zhimin Yin

Abstract

Heat-shock protein 27 (Hsp27) is a member of the small heat shock protein family that has been reported to protect cells against pro-inflammatory stresses. High mobility group box 1 (HMGB1) is a proinflammatory cytokine associated with death from sepsis and other inflammatory diseases. After being acetylated by CREB-binding protein (CBP), the transcriptional adaptor and acetyltransferase, HMGB1 translocates from the nucleus to the cytoplasm. In the present study, we investigated the effects of Hsp27 on HMGB1 translocation from the nucleus to the cytoplasm in THP-1 cells. We found that Hsp27 phosphorylation decreased LPS-induced HMGB1 acetylation and translocation from the nucleus to the cytoplasm, as well as its release from THP-1 cells. The study further showed that cytosolic non-phosphorylated Hsp27 enhanced CBP ubiquitination and degradation in LPS-unstimulated cells, which suggested that Hsp27 maintained suitable CBP levels under normal physiological conditions. After LPS stimulation, Hsp27 was phosphorylated at serine residues 15/78 and translocated from the cytoplasm into the nucleus. Consequently, LPS stimulation increased CBP levels and promoted its translocation into the nucleus. In the nucleus, Hsp27 bound to CBP and suppressed CBP acetyltransferase activity and the subsequent CBP-dependent acetylation of HMGB1. Taken together, our data demonstrated that cytosolic non-phosphorylated Hsp27 enhanced the ubiquitin-mediated degradation of CBP, while phosphorylated Hsp27 inhibited CBP acetyltransferase activity in the nucleus. By regulating CBP, Hsp27 maintained cell homeostasis and inhibited excessive inflammatory response.

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