A mutation in aminopeptidase N (CD13) isolated from a patient suffering from leukemia leads to an arrest in the endoplasmic reticulum.

Abstract

Human aminopeptidase N (APN) is used as a routine marker for myelomonocytic cells in hematopoietic malignant disorders. Its gene and surface expressions are increased in cases of malignant transformation, inflammation, or T cell activation, whereas normal B and resting T cells lack detectable APN protein expression. In this study we elucidated the intracellular distribution, expression pattern, and enzymatic activity of a naturally occurring mutation in the coding region of the APN gene. At physiological temperatures the mutant protein is enzymatically inactive, persists as a mannose-rich polypeptide in the endoplasmic reticulum, and is ultimately degraded by an endoplasmic reticulum-associated degradation pathway. It shows in part the distinct behavior of a temperature-sensitive mutant with a permissive temperature of 32 degrees C, leading to correct sorting of the Golgi compartment accompanied by the acquisition of proper glycosylation but without reaching the cell-surface membrane and without regaining its enzymatic activity. Because the patient bearing this mutation suffered from leukemia, possible links to the pathogenesis of leukemia are discussed.

• Authors: Marwan Alfalah, Michael P Krahn, Gabi Wetzel, Stephan von Hörsten, Carmen Wolke, Nigel Hooper, Thomas Kalinski, Sabine Krueger, Hassan Y Naim, Uwe Lendeckel
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 281 Issue 17 Pg. 11894-900 (Apr 28 2006) ISSN: 0021-9258 [Print] United States
• PMID: 16469741 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CD13 Antigens

Topics

• Aged
• Animals
• Bone Neoplasms (genetics, metabolism, secondary)
• CD13 Antigens (genetics, metabolism)
• COS Cells (metabolism)
• Carcinoma, Renal Cell (genetics, metabolism, pathology)
• Chlorocebus aethiops
• Endoplasmic Reticulum (metabolism)
• Glycosylation
• Golgi Apparatus (metabolism)
• Humans
• Kidney Neoplasms (genetics, metabolism, pathology)
• Lymphoma, Non-Hodgkin (genetics, metabolism, pathology)
• Male
• Mutation (genetics)
• Tumor Cells, Cultured