Nuclear Receptor Small Heterodimer Partner in Apoptosis Signaling and Liver Cancer

Small heterodimer partner (SHP, NR0B2) is a unique orphan nuclear receptor that contains the dimerization and a putative ligand-binding domain, but lacks the conserved DNA binding domain. SHP exerts its physiological function as an inhibitor of gene transcription through physical interaction with multiple nuclear receptors and transcriptional factors. SHP is a critical transcriptional regulator affecting diverse biological functions, including bile acid, cholesterol and lipid metabolism, glucose and energy homeostasis, and reproductive biology. Recently, we and others have demonstrated that SHP is an epigenetically regulated transcriptional repressor that suppresses the development of liver cancer. In this review, we summarize recent major findings regarding the role of SHP in cell proliferation, apoptosis, and DNA methylation, and discuss recent progress in understanding the function of SHP as a tumor suppressor in the development of liver cancer. Future study will be focused on identifying SHP associated novel prooncogenes and anti-oncogenes in liver cancer progression and applying the knowledge gained on SHP in liver cancer prevention, diagnosis and treatment.