Unraveling the mystery: How bad is BAG3 in hematological malignancies?

Biochim Biophys Acta Rev Cancer. 2022 Sep;1877(5):188781. doi: 10.1016/j.bbcan.2022.188781. Epub 2022 Aug 17.

Abstract

BAG3, also known as BIS and CAIR-1, interacts with Hsp70 via its BAG domain and with other molecules through its WW domain, PXXP repeats and IPV motifs. BAG3 can participate in major cellular pathways including apoptosis, autophagy, cytoskeleton structure, and motility by regulating the expression, location, and activity of its chaperone proteins. As a multifunctional protein, BAG3 is highly expressed in skeletal muscle, cardiomyocytes and multiple tumors, and its intracellular expression can be stimulated by stress. The functions and mechanisms of BAG3 in hematological malignancies have recently been a topic of interest. BAG3 has been confirmed to be involved in the development and chemoresistance of hematological malignancies and to act as a prognostic indicator. Modulation of BAG3 and its corresponding proteins has thus emerged as a promising therapeutic and experimental target. In this review, we consider the characteristics of BAG3 in hematological malignancies as a reference for further clinical and fundamental investigations.

Keywords: Apoptosis; Autophagy; BAG3; Chemoresistance; Hematological malignancy; Prognosis.

Publication types

  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing* / genetics
  • Adaptor Proteins, Signal Transducing* / metabolism
  • Apoptosis Regulatory Proteins* / genetics
  • Apoptosis Regulatory Proteins* / metabolism
  • Autophagy / physiology
  • HSP70 Heat-Shock Proteins / metabolism
  • Hematologic Neoplasms* / drug therapy
  • Hematologic Neoplasms* / genetics
  • Humans

Substances

  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • BAG3 protein, human
  • HSP70 Heat-Shock Proteins