Abstract
Survivin is a member of the IAP (inhibitor of apoptosis) gene family and is markedly overexpressed exclusively in cancers but not in normal adult tissues [1-7] implying that it could be an ideal target for cancer directed therapy. Strong expression of survivin in tumors correlates with a poor cancer treatment response and poor outcomes.
Notably, survivin is also present in some nonmalignant cells such as myeloid stem cells and peripheral blood mononuclear cells, T lymphocytes [6], melanocytes [8] and in hyperplastic polyps and sessile serrated adenomas [9]. Furthermore, survivin is widely expressed during embryogenesis in many tissues like human fetal lungs, liver, heart, kidney and gastrointestinal tract [5].
Apart from its role in antiapoptosis, survivin also plays a critical role in regulating the cell cycle at mitosis. To prevent apoptosis, survivin interacts with many regulatory factors [10].
Survivin is a small protein (displaying approximately 16.5-kDa band on SDS electrophoresis) and contains a single baculovirus IAP repeat but no RING finger motif, found in other IAP protein members. It is generally thought that transcriptional deregulation is a major mechanism involved in the aberrant expression of survivin in cancers.
Transcription of the survivin gene proceeds from a single promoter but 5 splicing isoforms arise from the primary transcript [3]. The common survivin isoform contains 4 exons and isoform ΔEx3 (lacking exon 3) interacts with 4-exon survivin in the mitochondria where they inhibit mitochondrial-dependent apoptosis.
Other survivin splice variants also colocalize with survivin in the mitochondria [3].