Single-stranded DNA-binding proteins regulate the abundance of LIM domain and LIM domain-binding proteins

被引:70
作者
Xu, Zhixiong
Meng, Xianzhang
Cai, Ying
Liang, Hong
Nagarajan, Lalitha
Brandt, Stephen J. [1 ]
机构
[1] Vanderbilt Univ, Dept Med, Nashville, TN 37232 USA
[2] Univ Texas, MD Anderson Canc Ctr, Grad Sch Biomed Sci, Program Genes & Dev,Dept Mol Genet, Houston, TX 77030 USA
[3] Vanderbilt Univ, Dept Cell & Dev Biol, Nashville, TN 37232 USA
[4] Vanderbilt Univ, Dept Canc Biol, Nashville, TN 37232 USA
[5] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA
[6] VA Tennessee Valley Healthcare Syst, Nashville, TN 37212 USA
关键词
single-stranded DNA-binding proteins; LIM domain proteins; LIM domain; binding proteins; ubiquitination; transcription factors; erythroid differentiation;
D O I
10.1101/gad.1528507
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The LIM domain-binding protein Ldb1 is an essential cofactor of LIM-homeodomain (LIM-HD) and LIM-only (LMO) proteins in development. The stoichiometry of Ldb1, LIM- HD, and LMO proteins is tightly controlled in the cell and is likely a critical determinant of their biological actions. Single-stranded DNA-binding proteins (SSBPs) were recently shown to interact with Ldb1 and are also important in developmental programs. We establish here that two mammalian SSBPs, SSBP2 and SSBP3, contribute to an erythroid DNA-binding complex that contains the transcription factors Tal1 and GATA-1, the LIM domain protein Lmo2, and Ldb1 and binds a bipartite E-box-GATA DNA sequence motif. In addition, SSBP2 was found to augment transcription of the Protein 4.2 (P4.2) gene, a direct target of the E-box-GATA-binding complex, in an Ldb1-dependent manner and to increase endogenous Ldb1 and Lmo2 protein levels, E-box-GATA DNA-binding activity, and P4.2 and beta-globin expression in erythroid progenitors. Finally, SSBP2 was demonstrated to inhibit Ldb1 and Lmo2 interaction with the E3 ubiquitin ligase RLIM, prevent RLIM-mediated Ldb1 ubiquitination, and protect Ldb1 and Lmo2 from proteasomal degradation. These results define a novel biochemical function for SSBPs in regulating the abundance of LIM domain and LIM domain-binding proteins.
引用
收藏
页码:942 / 955
页数:14
相关论文
共 53 条
  • [1] AGULNICK AD, 1996, NATURE, V384, P370
  • [2] Mechanism and function of deubiquitinating enzymes
    Amerik, AY
    Hochstrasser, M
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2004, 1695 (1-3): : 189 - 207
  • [3] LMO3 interacts with neuronal transcription factor, HEN2, and acts as an oncogene in neuroblastoma
    Aoyama, M
    Ozaki, T
    Inuzuka, H
    Tomotsune, D
    Hirato, J
    Okamoto, Y
    Tokita, H
    Ohira, M
    Nakagawara, A
    [J]. CANCER RESEARCH, 2005, 65 (11) : 4587 - 4597
  • [4] Single-strand-DNA-binding factors specifically recognize the pyrimidine element in the chick alpha 2(I) collagen gene promoter
    Bayarsaihan, D
    Lukens, LN
    [J]. BIOCHEMICAL JOURNAL, 1996, 314 : 293 - 296
  • [5] Stabilization and activation of p53 by the coactivator protein TAFII31
    Buschmann, T
    Lin, YH
    Aithmitti, N
    Fuchs, SY
    Lu, H
    Resnick-Silverman, L
    Manfredi, JJ
    Ronai, Z
    Wu, XW
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (17) : 13852 - 13857
  • [6] The Caenorhabditis elegans Ldb/NLI/Clim orthologue ldb-1 is required for neuronal function
    Cassata, G
    Röhrig, S
    Kuhn, F
    Hauri, HP
    Baumeister, R
    Bürglin, TR
    [J]. DEVELOPMENTAL BIOLOGY, 2000, 226 (01) : 45 - 56
  • [7] A novel, evolutionarily conserved gene family with putative sequence-specific single-stranded DNA-binding activity
    Castro, P
    Liang, H
    Liang, JC
    Nagarajan, L
    [J]. GENOMICS, 2002, 80 (01) : 78 - 85
  • [8] Ssdp proteins interact with the LIM-domain-binding protein Ldb1 to regulate development
    Chen, L
    Segal, D
    Hukriede, NA
    Podtelejnikov, AV
    Bayarsaihan, D
    Kennison, JA
    Ogryzko, VV
    Dawid, IB
    Westphal, H
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (22) : 14320 - 14325
  • [9] Chervinsky DS, 1999, MOL CELL BIOL, V19, P5025
  • [10] Xenopus Xlmo4 is a GATA cofactor during ventral mesoderm formation and regulates Ldb1 availability at the dorsal mesoderm and the neural plate
    de la Calle-Mustienes, E
    Lu, ZX
    Cortés, M
    Andersen, B
    Modolell, J
    Gómez-Skarmeta, JL
    [J]. DEVELOPMENTAL BIOLOGY, 2003, 264 (02) : 564 - 581