Kalyani Ruthala" /> *" /> Kalyani Ruthala, Jogeswar Gadi, Ji-Yeon Lee, Heejei Yoon, Hyun Joo Chung, and Myoung Hee Kim*" /> Kalyani Ruthala, Jogeswar Gadi, Ji-Yeon Lee, Heejei Yoon, Hyun Joo Chung, and Myoung Hee Kim*. Mol. Cells 2011;32:273-9. https://doi.org/10.1007/s10059-011-0069-8">
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Mol. Cells 2011; 32(3): 273-279

Published online September 30, 2011

https://doi.org/10.1007/s10059-011-0069-8

© The Korean Society for Molecular and Cellular Biology

Hoxc8 Downregulates Mgl1 Tumor Suppressor Gene Expression and Reduces Its Concomitant Function on Cell Adhesion

Kalyani Ruthala, Jogeswar Gadi1, Ji-Yeon Lee, Heejei Yoon, Hyun Joo Chung, and Myoung Hee Kim*

Department of Anatomy, Embryology Laboratory, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea, 1Institute of Endocrinology, Yonsei University College of Medicine, Seoul 120-752, Korea

Correspondence to : *Correspondence: mhkim1@yuhs.ac

Received: April 16, 2011; Revised: June 15, 2011; Accepted: June 20, 2011

Abstract

Hoxc8 is a homeobox gene family member, which is es-sential for growth and differentiation. Mgl1, a mouse homologue of the Drosophila tumor suppressor gene lgl, was previously identified as a possible target of Hoxc8. However, the biological effects and underlying molecular mechanism of Hoxc8 regulation on Mgl1 has not been fully established. The endogenous expression patterns of Hoxc8 were inversely correlated with those of Mgl1 in different types of cells and tissues. Here we showed that Hoxc8 overexpression downregulated the Mgl1 mRNA expression. Characterization of the ~2 kb Mgl1 promoter region revealed that the upstream sequence contains several putative Hox core binding sites and chromatin immunoprecipitation assay confirmed that Hoxc8 directly binds to the 5' upstream region of Mgl1. The promoter activity of this region was diminished by Hoxc8 expression but resumed by knockdown of Hoxc8 using siRNA against Hoxc8. Functional study of Mgl1 in C3H10T1/2 cells revealed a significant reduction in cell adhesion upon expression of Hoxc8. Taken together, our data suggest that Hoxc8 downregulates Mgl1 expression via direct binding to the promoter region, which in turn reduces cell adhesion and concomitant cell migration.

Keywords cell adhesion, direct downstream target gene, Hoxc8, Mgl1, tumor suppressor

Article

Research Article

Mol. Cells 2011; 32(3): 273-279

Published online September 30, 2011 https://doi.org/10.1007/s10059-011-0069-8

Copyright © The Korean Society for Molecular and Cellular Biology.

Hoxc8 Downregulates Mgl1 Tumor Suppressor Gene Expression and Reduces Its Concomitant Function on Cell Adhesion

Kalyani Ruthala, Jogeswar Gadi1, Ji-Yeon Lee, Heejei Yoon, Hyun Joo Chung, and Myoung Hee Kim*

Department of Anatomy, Embryology Laboratory, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea, 1Institute of Endocrinology, Yonsei University College of Medicine, Seoul 120-752, Korea

Correspondence to:*Correspondence: mhkim1@yuhs.ac

Received: April 16, 2011; Revised: June 15, 2011; Accepted: June 20, 2011

Abstract

Hoxc8 is a homeobox gene family member, which is es-sential for growth and differentiation. Mgl1, a mouse homologue of the Drosophila tumor suppressor gene lgl, was previously identified as a possible target of Hoxc8. However, the biological effects and underlying molecular mechanism of Hoxc8 regulation on Mgl1 has not been fully established. The endogenous expression patterns of Hoxc8 were inversely correlated with those of Mgl1 in different types of cells and tissues. Here we showed that Hoxc8 overexpression downregulated the Mgl1 mRNA expression. Characterization of the ~2 kb Mgl1 promoter region revealed that the upstream sequence contains several putative Hox core binding sites and chromatin immunoprecipitation assay confirmed that Hoxc8 directly binds to the 5' upstream region of Mgl1. The promoter activity of this region was diminished by Hoxc8 expression but resumed by knockdown of Hoxc8 using siRNA against Hoxc8. Functional study of Mgl1 in C3H10T1/2 cells revealed a significant reduction in cell adhesion upon expression of Hoxc8. Taken together, our data suggest that Hoxc8 downregulates Mgl1 expression via direct binding to the promoter region, which in turn reduces cell adhesion and concomitant cell migration.

Keywords: cell adhesion, direct downstream target gene, Hoxc8, Mgl1, tumor suppressor

Mol. Cells
Aug 31, 2022 Vol.45 No.8, pp. 513~602
COVER PICTURE
Cryo-EM structure of human porphyrin transporter ABCB6 (main figure) shows that binding of hemin (inset, magenta) in concert with two glutathione molecules (cyan) primes ABCB6 for high ATP turnover (Kim et al., pp. 575-587).

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