|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 277, Issue 51, 49488-49494, December 20, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Department of Biochemistry and Molecular Biology, The
University of Texas M. D. Anderson Cancer Center, Houston, Texas
77030
PAX6 functions as a transcription factor and has
two DNA-binding domains, a paired domain (PD) and a homeodomain
(HD), joined by a glycine-rich linker and followed by a
proline-serine-threonine-rich (PST) transactivation region at the C
terminus. The mechanism of PAX6 function is not clearly understood, and
few target genes in vertebrates have been identified. In this report we
described the functional analyses of patient missense mutations from
the paired domain region of PAX6 and a paireddomain-less isoform
(PD-less) of Pax6 that lacks the paired domain and part of the
glycine-rich linker. The PD-less was expressed in the brain, eyes, and
pancreas of mouse. The level of expression of this isoform was
relatively higher in brain. The mutation sites PAX6-L46R and -C52R were
located in the PD of PAX6 on either end of the 5a-polypeptide insert of the alternatively spliced form of PAX6, PAX6-5a. Another PAX6 mutant
V53L described in this report was adjacent to C52R. We created
corresponding mutations in PAX6 and PAX6-5a, and evaluated their
transcriptional activation and DNA binding properties. The PD mutants
of PAX6 (L46R, C52R, and V53L) exhibited lower transactivation activities and variable DNA binding ability than wild-type PAX6 with PD
DNA-binding consensus sequences. The mutated amino acids containing
PAX6-5a isoforms showed unexpected transactivation properties with a
reporter containing HD DNA-binding sequences. PAX6-5a-C52R, and -V53L
showed lower transactivation activities, but PAX6-5a-L46R had greater
transactivation ability than PAX6-5a. The PD-less isoform of Pax6 lost
its transactivational ability but could bind to the HD DNA-binding
sequences. Functional analysis of the PD-less isoform of Pax6 as
well as findings related to missense mutations in the PD suggest that
the PD of PAX6 is required for HD function.
PAX6, Paired Domain Influences Sequence Recognition by the
Homeodomain*
*
This research was supported by National Institutes of Health
Grants EY09675, EY10608, and CA 16672.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
Biochemistry and Molecular Biology, Box 117, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030. Tel.: 713-792-2690; Fax: 713-791-9478; E-mail:
gsaunders@odin.mdacc.tmc.edu.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Favor, C. J. Gloeckner, A. Neuhauser-Klaus, W. Pretsch, R. Sandulache, S. Saule, and I. Zaus Relationship of Pax6 Activity Levels to the Extent of Eye Development in the Mouse, Mus musculus Genetics, July 1, 2008; 179(3): 1345 - 1355. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. A. Kim, Y. T. Noh, M.-J. Ryu, H.-T. Kim, S.-E. Lee, C.-H. Kim, C. Lee, Y. H. Kim, and C. Y. Choi Phosphorylation and Transactivation of Pax6 by Homeodomain-interacting Protein Kinase 2 J. Biol. Chem., March 17, 2006; 281(11): 7489 - 7497. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-A. Bruun, E. I. S. Thomassen, K. Kristiansen, G. Tylden, T. Holm, I. Mikkola, G. Bjorkoy, and T. Johansen The third helix of the homeodomain of paired class homeodomain proteins acts as a recognition helix both for DNA and protein interactions Nucleic Acids Res., May 10, 2005; 33(8): 2661 - 2675. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Azuma, K. Tadokoro, A. Asaka, M. Yamada, Y. Yamaguchi, H. Handa, S. Matsushima, T. Watanabe, Y. Kida, T. Ogura, et al. Transdifferentiation of the retinal pigment epithelia to the neural retina by transfer of the Pax6 transcriptional factor Hum. Mol. Genet., April 15, 2005; 14(8): 1059 - 1068. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Haubst, J. Berger, V. Radjendirane, J. Graw, J. Favor, G. F. Saunders, A. Stoykova, and M. Gotz Molecular dissection of Pax6 function: the specific roles of the paired domain and homeodomain in brain development Development, December 15, 2004; 131(24): 6131 - 6140. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. N. Cinar and A. D. Chisholm Genetic Analysis of the Caenorhabditis elegans pax-6 Locus: Roles of Paired Domain-Containing and Nonpaired Domain-Containing Isoforms Genetics, November 1, 2004; 168(3): 1307 - 1322. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. K. Chauhan, Y. Yang, K. Cveklova, and A. Cvekl Functional interactions between alternatively spliced forms of Pax6 in crystallin gene regulation and in haploinsufficiency Nucleic Acids Res., March 12, 2004; 32(5): 1696 - 1709. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. K. Chauhan, Y. Yang, K. Cveklova, and A. Cvekl Functional Properties of Natural Human PAX6 and PAX6(5a) Mutants Invest. Ophthalmol. Vis. Sci., February 1, 2004; 45(2): 385 - 392. [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 |