DnaJ/HSP40 Homolog Subfamily A, Member 4 (DNAJA4)

DnaJA4 is a SREBP-regulated chaperone involved in the cholesterol biosynthesis pathway. DnaJA4, as a new SREBP-responsive gene. DnaJA4 was overexpressed in COS cells, which induced a specific increase in the synthesis of cholesterol from acetate. DnaJA4 overexpression increased the activity and the protein content of HMG-CoA reductase, the rate limiting enzyme in this pathway. At the molecular level, DnaJA4 overexpression did not alter HMG-CoA reductase stability or mRNA levels, suggesting a co-translational effect of the chaperone. In the DnaJ/Hsp40 family, DnaJA4 uniquely exhibited SREBP-regulated expression, and also responded to heat shock. Through its responsiveness to SREBP, and its stimulatory effect on cholesterol synthesis, the DnaJA4 chaperone can be viewed as a new player in cholesterol synthesis.