Regulation of major histocompatibility complex class I molecule expression on cancer cells by amyloid precursor-like pro
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Regulation of major histocompatibility complex class I molecule expression on cancer cells by amyloid precursor-like protein 2 Haley L. Peters • Amit Tuli • Mahak Sharma Naava Naslavsky • Steve Caplan • Richard G. MacDonald • Joyce C. Solheim
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Published online: 9 August 2011 Ó Springer Science+Business Media, LLC 2011
Abstract The three members of the amyloid precursor protein family in mammals [amyloid precursor protein, amyloid precursor-like protein 1, and amyloid precursorlike protein 2 (APLP2)] have been implicated in a large array of intracellular processes, which include development, transcription, apoptosis, metabolism, and the cell cycle. A series of studies by our laboratories has demonstrated that APLP2 is highly expressed by many cancer cell lines (with the highest expression in pancreatic cancer cell lines) and that it facilitates major histocompatibility complex (MHC) class I molecule endocytosis. This review focuses on this recently revealed function of APLP2 relevant to tumor immunology: that it acts as a novel regulator of MHC class I molecule surface expression. Keywords Amyloid precursor-like protein 2 Antigen presentation Cancer Endocytosis Major histocompatibility complex class I molecule Human leukocyte antigen Tumor antigen Tumor immunology Trafficking H. L. Peters A. Tuli S. Caplan R. G. MacDonald J. C. Solheim (&) Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA e-mail: [email protected] Present Address: A. Tuli M. Sharma Division of Rheumatology, Immunology, and Allergy, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA A. Tuli M. Sharma N. Naslavsky S. Caplan R. G. MacDonald J. C. Solheim Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA
Amyloid precursor-like protein 2 In the amyloid precursor protein (APP) family in mammals, there are three members: amyloid precursor protein (APP), amyloid precursor-like protein 1 (APLP1), and amyloid precursor-like protein 2. APP, containing the pathogenic beta-amyloid domain implicated in Alzheimer’s disease, is the most studied of the three, but there is an increasing amount of knowledge about the functions of the other two members, particularly APLP2. There is growing understanding that at least two of the members of this family, APP and APLP2, have multiple functions that potentially influence the biology of tumor cells. For example, APLP2 is involved in cellular functions as diverse as signaling, adhesion, migration, and mitosis [1– 6]. Although APLP1 expression is primarily limited to the nervous system, APP and APLP2 are ubiquitously expressed [7, 8]. The APP, APLP1, and APLP2 proteins all share a high degree of sequence similarity; however, the region of APP most implicated in Alzheimer’s disease (the amyloid peptide) is not shared with APLP1 and APLP2 [9]. Like APP, APLP2 exists as several isoforms of a type I transmembrane protein that is glycosylat
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