Novel regulation of the helix-loop-helix protein Id1 by S5a, a subunit of the 26 S proteasome.
Id proteins negatively regulate the dimerization, DNA binding, and biological properties of basic helix-loop-helix proteins. In a search for novel factors that interact with Id1, we identified a component of the 26 S proteasome, S5a, that has previously been implicated only in the recognition of ubiquitinated polypeptides destined for proteolysis. S5a interacts strongly with Id1, less strongly with the basic helix-loop-helix proteins MyoD and E12, and not at all with other Id proteins. S5a restores DNA binding by MyoD-Id1 and E12-Id1 heterodimers, enhances DNA binding by MyoD and E12 homodimers, and reverses Id1-mediated repression of the muscle creatine kinase promoter during myogenic differentiation. Mutagenesis experiments showed that amino acids flanking the helix-loop-helix domain plus three residues in the first helix of Id1 impart S5a recognition. This requires only the NH2-terminal half of S5a. S5a thus appears to promote the positive regulation of myogenic genes through ubiquitin-independent mechanisms involving inhibition of Id1 and the enhancement of DNA binding by MyoD and E12. This latter property may permit the selection of novel promoter binding sites during myogenesis.
Anand
G
G
Section of Hematology/Oncology, Department of Pediatrics, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
Yin
X
X
Shahidi
A K
AK
Grove
L
L
Prochownik
E V
EV
D000595:Amino Acid Sequence; D001483:Base Sequence; D004247:DNA / Q000378:metabolism; D006367:HeLa Cells; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1; D008969:Molecular Sequence Data; D009132:Muscles / Q000502:physiology*; D017570:MyoD Protein / Q000378:metabolism; D010447:Peptide Hydrolases / Q000502:physiology*; D011401:Promoter Regions, Genetic; D046988:Proteasome Endopeptidase Complex; D012097:Repressor Proteins; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*
C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D017570:MyoD Protein; D012097:Repressor Proteins; D014157:Transcription Factors; D004247:DNA; D010447:Peptide Hydrolases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease