ABSTRACT
Cullin 3 (CUL3) serves as a scaffold protein and assembles a large number of ubiquitin ligase complexes. It is involved in multiple cellular processes and plays a potential role in tumor development and progression. In this study, we demonstrate that CUL3 targets methionine adenosyltransferase IIα (MAT IIα) and promotes its proteasomal degradation through the ubiquitylation-mediated pathway. MAT IIα is a key enzyme in methionine metabolism and is associated with uncontrolled cell proliferation in cancer. We presently found that CUL3 down-regulation could rescue folate deprivation-induced MAT IIα exhaustion and growth arrest in colorectal cancer (CRC) cells. Further results from human CRC samples display an inverse correlation between CUL3 and MAT IIα protein levels. Our observations reveal a novel role of CUL3 in regulating cell proliferation by controlling the stability of MAT IIα.
Subject(s)
Colorectal Neoplasms/enzymology , Cullin Proteins/metabolism , Methionine Adenosyltransferase/metabolism , Blotting, Western , Cell Proliferation/drug effects , Cell Proliferation/genetics , Colorectal Neoplasms/genetics , Colorectal Neoplasms/physiopathology , Cullin Proteins/genetics , Folic Acid/genetics , Folic Acid/metabolism , HCT116 Cells , HEK293 Cells , Histone Deacetylase Inhibitors/pharmacology , Humans , Immunoprecipitation , In Vitro Techniques , Methionine Adenosyltransferase/chemistry , Methionine Adenosyltransferase/genetics , Proteolysis , RNA Interference , Ubiquitination/drug effects , Ubiquitination/geneticsABSTRACT
OBJECTIVE: To evaluate the reliability and validity of musculoskeletal questionnaire. METHODS: A self-administered modified musculoskeletal questionnaire was used to investigate 12 098 workers from eight occupations, i.e. coal mining, petroleum, metallurgical, mechanical manufacturing, chemical, garment and railroad transportation industries and education. The Cronbach's α coefficient, analysis of covariance and multiple logistic regression were used to assess the reliability and validity of musculoskeletal questionnaire. RESULTS: The consistent test between total items of Musculoskeletal Questionnaire and each factor showed that the range of Cronbach's α was 0.52 â¼ 0.92, except from vibration factor, other Cronbach's α was more than 0.7. All 55 items of Musculoskeletal Questionnaire were subjected to factor analysis, and ten latent factors were identified, which explained 55.17% of the total variance. The potentially hazardous working conditions could be categorized into seven dimensions (force, dynamic load, static load, repetitive load, climate factors, vibration exposure and environmental ergonomic factor), which consisted with the theory model. The results of covariance analysis indicated that there were significant difference among 7 dimension indices in different jobs (P < 0.01). CONCLUSION: The modified Musculoskeletal Questionnaire is a valid and reliable tool for measuring musculoskeletal workload.
