Expression and localization of inhibitor of apoptosis proteins in normal human tissues

Barbara Vischioni1, Paul van der Valk, Simone W Span

  • 1Department of Medical Oncology, VU University Medical Center, HV1081 Amsterdam, The Netherlands.

Human Pathology
|December 20, 2005
PubMed

Insights

Inhibitors of apoptosis (IAPs) are widely expressed in normal human tissues at the protein level, not just mRNA. Their varying expression and localization suggest a physiological role, crucial for developing targeted cancer therapies.

Area of Science:

  • Cellular biology
  • Molecular oncology
  • Cancer research

Background:

  • Inhibitor of apoptosis (IAP) proteins, including cIAP1, cIAP2, and XIAP, are known to suppress apoptosis.
  • While survivin is typically absent in normal adult tissues, cIAP1, cIAP2, and XIAP are broadly expressed at the mRNA level in normal cells.
  • Expression of these IAPs and survivin has been linked to tumor markers and patient prognosis in cancer.

Purpose of the Study:

  • To investigate the protein-level expression of IAPs across a comprehensive panel of normal human tissues.
  • To determine if IAP expression and localization patterns vary by cell lineage.
  • To explore the implications of IAP expression and localization for their physiological roles and cancer therapy.

Main Methods:

  • Immunohistochemical analysis of IAP protein expression.
  • Examination of a wide range of normal human tissue samples.
  • Assessment of subcellular localization of IAPs within different cell types.

Main Results:

  • Confirmed broad expression of IAP proteins at the tissue level, consistent with previous mRNA findings.
  • Demonstrated distinct IAP expression levels and subcellular localization patterns across different cell lineages.
  • Identified variable compartmentalization of IAPs, suggesting a regulatory mechanism for their function.

Conclusions:

  • IAP proteins play a physiological role in normal human cells, with expression varying by cell type and location.
  • Understanding IAP compartmentalization is key to elucidating their function.
  • Further research into the physiological roles of IAPs is essential for refining IAP-targeted cancer therapies and minimizing side effects.

Related Concept Videos

The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...