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PMID: 17437998 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

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

Genes & development ·Vol. 21 ·No. 8 ·2007-04-15 ·Pages 942-55

Xu Z, Meng X, Cai Y, Liang H, Nagarajan L, Brandt SJ

Abstract

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.

MeSH Terms
Animals Beta-Globulins/genetics CHO Cells COS Cells Cell Line, Tumor Chlorocebus aethiops Cricetinae Cricetulus DNA, Single-Stranded/metabolism DNA-Binding Proteins/metabolism Erythroid Precursor Cells/chemistry GATA1 Transcription Factor/metabolism Homeodomain Proteins/metabolism Mice Multiprotein Complexes/metabolism Promoter Regions, Genetic Protein Structure, Tertiary RNA Interference Repressor Proteins/metabolism Transcription Factors/metabolism
Chemicals
Beta-Globulins DNA, Single-Stranded DNA-Binding Proteins GATA1 Transcription Factor Homeodomain Proteins Multiprotein Complexes Repressor Proteins Transcription Factors
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Xu Zhixiong
Department of Medicine, Vanderbilt University, Nashville, Tennessee 37232, USA.
Meng Xianzhang
Cai Ying
Liang Hong
Nagarajan Lalitha
Brandt Stephen J
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.1528507
Published
2007-04-15
Pages
942-55
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC1847712
Subset
IM
Grants
NHLBI NIH HHS · R01 HL049118 · United States
NHLBI NIH HHS · R01 HL49118 · United States
NHLBI NIH HHS · HL074449 · United States
NHLBI NIH HHS · R01 HL074449 · United States
NHLBI NIH HHS · R01 HL049118-14A2 · United States
External Links
PubMed source DOI: 10.1101/gad.1528507 PMC Full Text View journal details
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