Promyelocytic leukemia (PML) nuclear bodies are disorganized in colorectal tumors with total loss of major histocompatibility complex class I expression and LMP7 downregulation.
The promyelocytic leukemia (PML) protein is the product of the PML gene that fuses with the retinoic acid receptor-alpha (RARalpha) gene in acute promyelocytic leukemia (APL) and produces disruption of PML bodies. Wild-type PML localizes in the nucleus with a typical speckled pattern. PML bodies accumulate several proteins involved in multiple cellular pathways such as apoptosis, transcriptional regulation, and proteasomal degradation of ubiquitinated proteins. The ubiquitin-proteasome pathway at PML bodies is dependent on proteasome component recruitment. Proteasome components such as low-molecular weight proteins (LMPs) are frequently downregulated in different tumor tissues that present impaired major histocompatibility complex (MHC) class I expression. We have recently documented LMP7 downregulation in colorectal tumors with total loss of MHC class I antigen. An immunohistochemical study of PML protein in these tumors revealed a disrupted pattern of PML bodies in a nuclear diffuse form, as observed in APL cells. Therefore, the disruption of the PML bodies was clearly associated with LMP7 downregulation.
Cabrera
C M
CM
Departamento de Análisis Clínicos, Hospital Universitario Virgen de las Nieves, Avd. Fuerzas Armadas 2, 18014 Granada, Spain.
Jiménez
P
P
Concha
A
A
Garrido
F
F
Ruiz-Cabello
F
F
D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D009097:Multienzyme Complexes / Q000096:biosynthesis* / Q000235:genetics; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D000071156:Promyelocytic Leukemia Protein; D046988:Proteasome Endopeptidase Complex; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D015395:Histocompatibility Antigens Class I; D009097:Multienzyme Complexes; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex