GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:15314159

From GONUTS
Jump to: navigation, search
Citation

Schlaeger, TM, Schuh, A, Flitter, S, Fisher, A, Mikkola, H, Orkin, SH, Vyas, P and Porcher, C (2004) Decoding hematopoietic specificity in the helix-loop-helix domain of the transcription factor SCL/Tal-1. Mol. Cell. Biol. 24:7491-502

Abstract

The helix-loop-helix (HLH) domain is employed by many transcription factors that control cell fate choice in multiple developmental settings. Previously, we demonstrated that the HLH domain of the class II basic HLH (bHLH) protein SCL/Tal-1 is critical for hematopoietic specification. We have now identified residues in this domain that are essential for restoring hematopoietic development to SCL-/- embryonic stem cells and sufficient to convert a muscle-specific HLH domain to one able to rescue hematopoiesis. Most of these critical residues are distributed in the loop of SCL, with one in helix 2. This is in contrast to the case for MyoD, the prototype of class II bHLH proteins, where the loop seems to serve mainly as a linker between the two helices. Among the identified residues, some promote heterodimerization with the bHLH partners of SCL (E12/E47), while others, unimportant for this property, are still crucial for the biological function of SCL. Importantly, the residue in helix 2 specifically promotes interaction with a known partner of SCL, the LIM-only protein LMO2, a finding that strengthens genetic evidence that these proteins interact. Our data highlight the functional complexity of bHLH proteins, provide mechanistic insight into SCL function, and strongly support the existence of an active SCL/LMO2-containing multiprotein complex in early hematopoietic cells.

Links

PubMed PMC506978 Online version:10.1128/MCB.24.17.7491-7502.2004

Keywords

Adaptor Proteins, Signal Transducing; Amino Acid Sequence; Animals; Basic Helix-Loop-Helix Transcription Factors; Cell Line; Cell Lineage; DNA-Binding Proteins/chemistry; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Helix-Loop-Helix Motifs; Hematopoiesis/genetics; Hematopoiesis/physiology; LIM Domain Proteins; Macromolecular Substances; Metalloproteins/genetics; Metalloproteins/metabolism; Mice; Mice, Knockout; Molecular Sequence Data; Multiprotein Complexes; Mutation; Phenylalanine/metabolism; Protein Binding; Proto-Oncogene Proteins/chemistry; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/metabolism; Sequence Alignment; Stem Cells/physiology; Transcription Factors/chemistry; Transcription Factors/genetics; Transcription Factors/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:TFE2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:P22091

F

Seeded From UniProt

complete

MOUSE:TFE2

part_of

GO:0005667: transcription regulator complex

ECO:0000353: physical interaction evidence used in manual assertion

PR:P22091
PR:P25801

C

Seeded From UniProt

complete

MOUSE:TFE2

acts_upstream_of_or_within

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:98480

P

Seeded From UniProt

complete

MOUSE:TAL1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:P15806

F

Seeded From UniProt

complete

MOUSE:TAL1

acts_upstream_of_or_within

GO:0030218: erythrocyte differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

  • results_in_acquisition_of_features_of:(CL:0000232)

Seeded From UniProt

complete

MOUSE:TAL1

part_of

GO:0005667: transcription regulator complex

ECO:0000353: physical interaction evidence used in manual assertion

PR:P15806
PR:P25801

C

Seeded From UniProt

complete

MOUSE:TAL1

acts_upstream_of_or_within

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:98510

P

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.