Functional Compartmentalization of HSP60-Survivin Interaction between Mitochondria and Cytosol in Cancer Cells

Abstract

Heat shock protein 60 (HSP60) and survivin reside in both the cytosolic and mitochondrial compartments under physiological conditions. They can form HSP60-survivin complexes through protein-protein interactions. Their expression levels in cancer tissues are positively correlated and higher expression of either protein is associated with poor clinical prognosis. The subcellular location of HSP60-survivin complex in either the cytosol or mitochondria is cell type-dependent, while the biological significance of HSP60-survivin interaction remains elusive. Current knowledge indicates that the function of HSP60 partly rests on where HSP60-survivin interaction takes place. HSP60 has a pro-survival function when binding to survivin in the mitochondria through interacting with other factors such as CCAR2 and p53. In response to cell death signals, mitochondrial survivin functions through preventing procaspase activation. Degradation of cytosolic survivin leads to the loss of mitochondrial membrane potential and aberrant mitosis processes. On the other hand, HSP60 release from mitochondria to cytosol upon death stimuli might exert a pro-death function, either through stabilizing Bax, enhancing procaspase-3 activation, or increasing protein ubiquitination. Combining the knowledge of mitochondrial HSP60-survivin complex function, cytosolic survivin degradation effect, and pro-death function upon mitochondria release of HSP60, a hypothetical scenario for HSP60-survivin shuttling upon death stimuli is proposed.

HSPA4 knockdown retarded progression and development of colorectal cancer

“…On the one hand, Caspase3 is a major executioner caspase, active Caspase3 degrades multiple cellular proteins and is responsible for cell morphology changes and DNA fragmentation during apoptosis [19,20]. On the other hand, HSP60 released from mitochondria to cytosol upon death stimuli might exert a pro-death function, either through stabilizing Bax, enhancing Caspase3 activation, or increasing protein ubiquitination [21,22]. Moreover, Qiu et al, pointed that IGFBP-6 could inhibit invasion and migration of CRC cells possibly via promoting apoptosis activity and arresting cell cycle [23].…”

Promotion of ubiquitination-dependent survivin destruction contributes to xanthohumol-mediated tumor suppression and overcomes radioresistance in human oral squamous cell carcinoma

“…Previous reported showed that survivin is predominantly localized in the cytoplasm of cancer cells and is generally believed to function as apoptotic suppressor to maintain survival of cancer cells. In contrast, the smaller fraction of nuclear localized survivin is considered to act as a component of CPC complex to promote cell cycle progression, suggesting that the different subcellular pools of survivin exhibit distinct biological functions (13)(14)(15)(16). Thus, as an oncoprotein that is both essential for mitosis and apoptosis inhibition, survivin seemed a promising novel target for anti-cancer treatment.…”

Hspa4 Knockdown Retarded Progression and Development of Colorectal Cancer

“…released from mitochondria to cytosol upon death stimuli might exert a pro-death function, either through stabilizing Bax, enhancing Caspase3 activation, or increasing protein ubiquitination [21,22]. Moreover, Qiu et al, pointed that IGFBP-6 could inhibit invasion and migration of CRC cells possibly via promoting apoptosis activity and arresting cell cycle [23].…”