| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 276, Issue 22, 19020-19026, June 1, 2001
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Department of Cell and Developmental Biology, Oregon
Health Sciences University, Portland, Oregon 97201
Lhx3, a member of the LIM homeodomain family of
transcription factors, is required for development of the pituitary in
mice. A recent report has described a point mutation in the human
LHX3 gene that is associated with a combined pituitary
hormone disorder. The mutation is predicted to lead to the replacement
of a tyrosine residue with a cysteine in the second LIM domain of LHX3.
We have characterized the effects of this point mutation (Y114C) when analyzed in the context of the mouse Lhx3 coding sequence. Mobility shift assays demonstrated that the Lhx3 Y114C mutant is capable of
binding DNA, although a decrease in the formation of a specific complex
was observed. Transfection assays using an expression vector for either
full-length Lhx3 or a GAL4-Lhx3 LIM domain fusion provided evidence
that the Lhx3 Y114C mutant has a decreased ability to stimulate
transcription. In particular, a GAL4-Lhx3 Y114C LIM mutant was unable
to support Ras responsiveness of a modified glycoprotein hormone
A Point Mutation in the LIM Domain of Lhx3 Reduces Activation of
the Glycoprotein Hormone
-Subunit Promoter*
-subunit reporter gene. Protein interaction studies suggest that the
Y114C mutation may modestly reduce binding to the POU transcription
factor, Pit-1. Interestingly, the Y114C mutation essentially abrogated
binding to the putative co-activator/adapter, selective LIM-binding
protein. The findings provide insights into the mechanisms mediating
transcriptional activation by Lhx3 and suggest that the observed
phenotype of the human mutation probably involves reduced
transcriptional activity of the mutant LHX3.
*
This work was supported by National Institutes of Health
Grants DK36407 and DK40339 (to R. A. M).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of Cell and
Developmental Biology, Oregon Health Sciences University, 3181 S.W. Sam
Jackson Park Rd., Portland, OR 97201. Tel.: 503-494-7566; Fax:
503-494-4253; E-mail: maurerr@ohsu.edu.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  D. E. Montoya-Durango, C. S. Velu, A. Kazanjian, M. E. B. Rojas, C. M. Jay, G. D. Longmore, and H. L. Grimes Ajuba Functions as a Histone Deacetylase-dependent Co-repressor for Autoregulation of the Growth Factor-independent-1 Transcription Factor J. Biol. Chem., November 14, 2008; 283(46): 32056 - 32065. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Ayyanathan, H. Peng, Z. Hou, W. J. Fredericks, R. K. Goyal, E. M. Langer, G. D. Longmore, and F. J. Rauscher III The Ajuba LIM Domain Protein Is a Corepressor for SNAG Domain Mediated Repression and Participates in Nucleocytoplasmic Shuttling Cancer Res., October 1, 2007; 67(19): 9097 - 9106. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. W. Pfaeffle, J. J. Savage, C. S. Hunter, C. Palme, M. Ahlmann, P. Kumar, J. Bellone, E. Schoenau, E. Korsch, J. H. Bramswig, et al. Four Novel Mutations of the LHX3 Gene Cause Combined Pituitary Hormone Deficiencies with or without Limited Neck Rotation J. Clin. Endocrinol. Metab., May 1, 2007; 92(5): 1909 - 1919. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. P. S. Bhangoo, C. S. Hunter, J. J. Savage, H. Anhalt, S. Pavlakis, E. C. Walvoord, S. Ten, and S. J. Rhodes A Novel LHX3 Mutation Presenting as Combined Pituitary Hormonal Deficiency J. Clin. Endocrinol. Metab., March 1, 2006; 91(3): 747 - 753. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. C. Yaden, M. Garcia III, T. P. L. Smith, and S. J. Rhodes Two Promoters Mediate Transcription from the Human LHX3 Gene: Involvement of Nuclear Factor I and Specificity Protein 1 Endocrinology, January 1, 2006; 147(1): 324 - 337. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. E. West, G. E. Parker, J. J. Savage, P. Kiratipranon, K. S. Toomey, L. R. Beach, S. C. Colvin, K. W. Sloop, and S. J. Rhodes Regulation of the Follicle-Stimulating Hormone {beta} Gene by the LHX3 LIM-Homeodomain Transcription Factor Endocrinology, November 1, 2004; 145(11): 4866 - 4879. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Jorgensen, C. C. Quirk, and J. H. Nilson Multiple and Overlapping Combinatorial Codes Orchestrate Hormonal Responsiveness and Dictate Cell-Specific Expression of the Genes Encoding Luteinizing Hormone Endocr. Rev., August 1, 2004; 25(4): 521 - 542. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. W. Sloop, C. J. Dwyer, and S. J. Rhodes An Isoform-specific Inhibitory Domain Regulates the LHX3 LIM Homeodomain Factor Holoprotein and the Production of a Functional Alternate Translation Form J. Biol. Chem., September 21, 2001; 276(39): 36311 - 36319. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
