Journal
FASEB JOURNAL
Volume 25, Issue 7, Pages 2305-2312Publisher
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.10-177808
Keywords
myosin light chain kinase; human cancers; gene duplication; RNA stability
Categories
Funding
- NHLBI NIH HHS [P01 HL058064] Funding Source: Medline
Ask authors/readers for more resources
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 (similar to 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.-Han, Y. J., Ma, S. F., Yourek, G., Park, Y.-D., Garcia, J. G. N. A transcribed pseudogene of MYLK promotes cell proliferation. FASEB J. 25, 2305-2312 (2011). www.fasebj.org
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available