Ubiquitin ligases in malignant lymphoma.
The highly controlled degradation of proteins via the ubiquitin-proteasome pathway represents a key mechanism for cell regulation and homeostasis. Ubiquitin-dependent proteolysis, carried out in large part by the E3 ubiquitin ligases, is a critical mode of post-translational modification that is important in regulation of cell cycle progression, signal transduction, gene transcription, antigen receptor signaling, immune response and cell differentiation. Recent studies demonstrate that increasing numbers of proteins with ubiquitin ligase activity are being characterized. Identification and characterization of their substrates indicate that they regulate the turnover of key cell cycle proteins (p27Kip1, p21Cip1, p57Kip2, cyclin E), tumor suppressor proteins (p53, RB), signaling kinases (Src, Zap70, PI-3 kinase), apoptosis regulators (Bcl-2, Bax, Bik) and transcription factors (Myc, NF-kappaB, E1F1), all of which have been implicated in the pathogenesis of malignant lymphoma. Studies to determine the functional role of ubiquitin ligases in the pathogenesis of malignant lymphoma represent potential areas of investigation.
Lim
Megan S
MS
Division of Anatomic Pathology, Department of Pathology, University of Utah, Salt Lake City, Utah 84132, USA. megan.lim@path.utah.edu
Elenitoba-Johnson
Kojo S J
KS
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D018797:Cell Cycle Proteins / Q000502:physiology; D002471:Cell Transformation, Neoplastic; D003546:Cysteine Endopeptidases / Q000502:physiology; D010450:Endopeptidases / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D018398:Homeodomain Proteins / Q000502:physiology; D006801:Humans; D008223:Lymphoma / Q000201:enzymology* / Q000209:etiology; D048728:MAP Kinase Kinase Kinase 1; D020930:MAP Kinase Kinase Kinases / Q000502:physiology; D051379:Mice; D009097:Multienzyme Complexes / Q000502:physiology; D009363:Neoplasm Proteins / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex; D011494:Protein Kinases / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000502:physiology; D050721:Proto-Oncogene Proteins c-cbl; D044843:SKP Cullin F-Box Protein Ligases / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology; D043222:Ubiquitin Thiolesterase; D043743:Ubiquitin-Protein Ligase Complexes / Q000502:physiology; D044767:Ubiquitin-Protein Ligases / Q000502:physiology*; D000076084:Ubiquitin-Specific Peptidase 7
D018797:Cell Cycle Proteins; D018398:Homeodomain Proteins; D009097:Multienzyme Complexes; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; C064658:RAG-1 protein; D043743:Ubiquitin-Protein Ligase Complexes; D050721:Proto-Oncogene Proteins c-cbl; D044843:SKP Cullin F-Box Protein Ligases; D044767:Ubiquitin-Protein Ligases; D011494:Protein Kinases; D048728:MAP Kinase Kinase Kinase 1; D020930:MAP Kinase Kinase Kinases; C482576:MAP3K1 protein, human; C482578:Map3k1 protein, mouse; D010450:Endopeptidases; C464569:USP7 protein, human; D043222:Ubiquitin Thiolesterase; D000076084:Ubiquitin-Specific Peptidase 7; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C067419:CBL protein, human; C493849:Cbl protein, mouse