Angiogenin Interacts with Heat Shock Factor 1

Abstract

Angiogenin (ANG) and heat shock factor 1 (HSF1) function in distinct pathways to mediate cellular stress. HSF1, an evolutionarily highly conserved protein, plays a role in a multitude of cellular processes that includes responses to cell stress as well as development, metabolism, and aging. Upon stress in cells, monomeric HSF1 trimerizes, localizes to the nucleus, binds to heat shock elements (HSE), and activates transcription of chaperones, co-chaperones, and ubiquitin. ANG, a vertebrate-specific ribonuclease with potent angiogenic activity, possesses both RNA- and DNA-binding capacity. During cell stress it is activated to cleave the anticodon loops and CCA-3' ends of tRNA in order to stall translation, however, the protein and DNA targets of ANG that facilitate changes in gene expression are not known. In independent studies, both ANG and HSF1 have been found to bind to DNA sequences within pericentromeres. The goal of this study was to determine if ANG and HSF1 interact directly. Using pull-down experiments, we demonstrated a specific interaction between ANG and two distinct forms of HSF1. The mechanistic relationship between ANG and HSF1 is yet undiscovered and is the focus of our current work.