Cold Shock Proteins

Cold shock proteins are multifunctional RNA/DNA-binding proteins characterized by the presence of one or more cold shock domains. Cold shock proteins are components of ribonucleoprotein complexes. In humans, the best characterized members of this family are called Y-box-binding proteins.

The prototypical member is Y-box binding protein-1 (YB-1), also known as DNA binding protein B (DbpB), which is encoded by the gene YBX1. There are two other family members, DNA-binding protein A (DbpA) and C (DbpC), which are encoded by the YBX3 and YBX2 genes, respectively. While the expression of Ybx2 is restricted to the germ cells, Ybx1 and Ybx3 are ubiquitously expressed during development. After birth, however, the expression of Ybx3 (DbpA) is downregulated in most tissues, with the exception of the heart, skeletal muscle, blood vessels and testes. Another developmentally important cold shock protein expressed in humans is Lin28, which was first characterized as a developmental factor in C. elegans. CARHSP1 also belongs to the human cold shock proteins. CARHSP1 stands for: calcium-regulated heat-stable protein 1 and is a 24 kDa protein. The last member of this family is called Upstream of N-RAS (UNR).

Cold shock proteins are among the best conserved proteins in evolutionary terms. Their characteristic feature is the presence of one or more cold shock domains (CSD), which have nucleic acid-binding properties. This gives these proteins pleiotropic functions, such as the regulation of transcription, translation and splicing. Individual members of the cold shock protein family are constantly expressed. Others are not produced in response to cold stress, but are increased in response to other environmental influences. The biological activities range from regulating transcription, splicing and translation to controlling the content of exosomal RNA.

Cold shock proteins were first identified in bacteria in which a sudden drop in temperature (from 37 °C to 10 °C) caused a 200-fold increase in the expression of cold shock protein A (CspA) within minutes, which was independent of transcriptional activity. This rapid inducibility is the same in different species. Meanwhile, RNase R and CspA have been identified as the main players. RNase R appears to be responsible for the degradation of misfolded RNAs, while CspA targets double-stranded RNAs to enable translation.

1. Lindquist JA et al. (2018) Cold shock proteins: from cellular mechanisms to pathophysiology and disease. Cell Commun Signal 16:63.
2. Mirabile G et al. (2022) New Insights into Cold Shock Proteins Effects in Human Cancer: Correlation with Susceptibility, Prognosis and Therapeutical Perspectives. Curr Med Chem 29: 5965-5978.