Document Detail


A transcribed pseudogene of MYLK promotes cell proliferation.
MedLine Citation:
PMID:  21441351     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Pseudogenes are considered nonfunctional genomic artifacts of catastrophic pathways. Recent evidence, however, indicates novel roles for pseudogenes as regulators of gene expression. We tested the functionality of myosin light chain kinase pseudogene (MYLKP1) in human cells and tissues by RT-PCR, promoter activity, and cell proliferation assays. MYLKP1 is partially duplicated from the original MYLK gene that encodes nonmuscle and smooth muscle myosin light chain kinase (smMLCK) isoforms and regulates cell contractility and cytokinesis. Despite strong homology with the smMLCK promoter (∼ 89.9%), the MYLKP1 promoter is minimally active in normal bronchial epithelial cells but highly active in lung adenocarcinoma cells. Moreover, MYLKP1 and smMLCK exhibit negatively correlated transcriptional patterns in normal and cancer cells with MYLKP1 strongly expressed in cancer cells and smMLCK highly expressed in non-neoplastic cells. For instance, expression of smMLCK decreased (19.5 ± 4.7 fold) in colon carcinoma tissues compared to normal colon tissues. Mechanistically, MYLKP1 overexpression inhibits smMLCK expression in cancer cells by decreasing RNA stability, leading to increased cell proliferation. These studies provide strong evidence for the functional involvement of pseudogenes in carcinogenesis and suggest MYLKP1 as a potential novel diagnostic or therapeutic target in human cancers.
Authors:
Yoo Jeong Han; Shwu Fan Ma; Gregory Yourek; Yoon-Dong Park; Joe G N Garcia
Publication Detail:
Type:  Journal Article     Date:  2011-03-25
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  25     ISSN:  1530-6860     ISO Abbreviation:  FASEB J.     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-07-01     Completed Date:  2011-09-28     Revised Date:  2012-02-15    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2305-12     Citation Subset:  IM    
Affiliation:
Department of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612-7227, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Base Sequence
Blotting, Western
Cell Line
Cell Line, Tumor
Cell Proliferation*
Cells, Cultured
Chromosome Mapping
Chromosomes, Human, Pair 3 / genetics
Female
Gene Expression Regulation, Enzymologic
Gene Expression Regulation, Neoplastic
Humans
Luciferases / genetics,  metabolism
Molecular Sequence Data
Myosin-Light-Chain Kinase / genetics*,  metabolism
Promoter Regions, Genetic / genetics*
Pseudogenes / genetics*
Reverse Transcriptase Polymerase Chain Reaction
Sequence Homology, Amino Acid
Sequence Homology, Nucleic Acid
Transcription, Genetic
Chemical
Reg. No./Substance:
EC 1.13.12.-/Luciferases; EC 2.7.11.18/Myosin-Light-Chain Kinase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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