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apoptotic proteins

Wednesday 8 February 2006

Cell death by apoptosis is exerted by the coordinated action of many different gene products.


- Mutations in some of them, acting at different levels in the apoptosis process, have been identified as cause or contributing factor for human diseases.

- Defects in the transmembrane tumor necrosis factor receptor 1 (TNF-R1) lead to the development of familial periodic fever syndromes.

- Mutations in the homologous receptor Fas (also named CD95; Apo-1) are observed in malignant lymphomas, solid tumors and the autoimmune lymphoproliferative syndrome type I (ALPS I).

- A mutation in the ligand for Fas (Fas ligand; CD95 ligand, Apo-1 ligand), which induces apoptosis upon binding to Fas, was described in a patient with systemic lupus erythematodes and lymphadenopathy.

- Perforin, an other cytotoxic protein employed by T- and NK-cells for target cell killing, is mutated in chromosome 10 linked cases of familial hemophagocytic lymphohistiocytosis.

- Caspase 10, a representative of the caspase family of proteases, which plays a central role in the execution of apoptosis, is defect in autoimmune lymphoproliferative syndrome type II (ALPS II).

- The intracellular pro-apoptotic molecule bcl-10 (BCL10) is frequently mutated in mucosa-associated lymphoid tissue (MALT) lymphomas and various non-hematologic malignancies.

- The p53 (TP53), an executioner of DNA damage triggered apoptosis, and BAX, a pro-apoptotic molecule with the ability to perturb mitochondrial membrane integrity, are frequently mutated in malignant neoplasms.

- Anti-apoptotic proteins like BCL2, cellular-inhibitor of apoptosis protein 2 (c-IAP2) and neuronal apoptosis inhibitory protein 1 (NAIP1) are often altered in follicular lymphomas, MALT lymphomas and spinal muscular atrophy (SMA), respectively.


- Mullauer L, Gruber P, Sebinger D, Buch J, Wohlfart S, Chott A. Mutations in apoptosis genes: a pathogenetic factor for human disease. Mutat Res. 2001 Jul;488(3):211-31. PMID: 11397650