Interaction of a Paraneoplastic Cerebellar Degeneration-Associated Neuronal Protein with the Nuclear Helix-Loop-Helix Leucine Zipper Protein MRG X

Abstract The mi locus encodes a member of the basic-helix-loop-helix-leucine zipper protein family of transcription factors (hereafter called MITF). We have reported that expression of several genes was impaired in cultured mast cells (CMCs) ofmi/mi mice due to a defective transactivation ability of mutant MITF (mi-MITF). Because attachment of mi/mi CMCs to fibroblasts is impaired, we examined the expression of integrin genes in mi/mi CMCs in the present study. Among the integrin genes examined, the expression of integrin 4 subunit was barely detectable in mi/mi CMCs, and the 4 protein was not detected by flow cytometry either. The specific adhesion to vascular cell adhesion molecule-1 (VCAM-1), the ligand for 4 subunit, was observed in +/+ CMCs but not in mi/mi CMCs, indicating that the expression of integrin 4 subunit at a functional level did not occur in mi/mi CMCs. In the promoter region of the 4 subunit gene, there was a CACTTG motif to which normal MITF (+- MITF) bound. The coexpression of +-MITF but not of mi-MITF transactivated the promoter of the 4 subunit gene. The deletion or mutation of the CACTTG motif abolished the transactivation by +-MITF, suggesting that +-MITF directly transactivated the gene encoding 4 subunit of integrin. © 1998 by The American Society of Hematology.

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SREBP-2, a second basic-helix-loop-helix-leucine zipper protein that stimulates transcription by binding to a sterol regulatory element.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.90.24.11603 ◽

1993 ◽

Vol 90 (24) ◽

pp. 11603-11607 ◽

Cited By ~ 385

Author(s):

X. Hua ◽

C. Yokoyama ◽

J. Wu ◽

M. R. Briggs ◽

M. S. Brown ◽

...

Keyword(s):

Leucine Zipper ◽

Regulatory Element ◽

Basic Helix Loop Helix ◽

Helix Loop Helix ◽

Sterol Regulatory Element ◽

Leucine Zipper Protein

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Systematic Method to Obtain Novel Genes That Are Regulated bymi Transcription Factor: Impaired Expression of Granzyme B and Tryptophan Hydroxylase in mi/mi Cultured Mast Cells

Blood ◽

10.1182/blood.v91.9.3210.3210_3210_3221 ◽

1998 ◽

Vol 91 (9) ◽

pp. 3210-3221 ◽

Cited By ~ 5

Author(s):

Akihiko Ito ◽

Eiichi Morii ◽

Kazutaka Maeyama ◽

Tomoko Jippo ◽

Dae-Ki Kim ◽

...

Keyword(s):

Mast Cells ◽

Leucine Zipper ◽

Tryptophan Hydroxylase ◽

Serotonin Synthesis ◽

Systematic Method ◽

Serotonin Content ◽

Helix Loop Helix ◽

New Genes ◽

Rate Limiting ◽

Leucine Zipper Protein

The mi locus encodes a member of the basic-helix-loop-helix-leucine zipper protein family of transcription factors (hereafter called MITF). We have reported that the expression of several genes was impaired in cultured mast cells (CMCs) ofmi/mi genotype, and demonstrated the involvement of MITF in the transcription of these genes. To obtain new genes whose transcription may be regulated by MITF, we prepared a subtracted cDNA library using +/+ and mi/mi CMCs. We found two clones carrying the granzyme (Gr) B and tryptophan hydroxylase (TPH) cDNAs in the subtracted library. The expression of the Gr B and TPH genes decreased in mi/mi CMCs, and recovered to nearly normal level by the overexpression of normal (+) MITF but not of mutant (mi) MITF. The +-MITF bound three and one CANNTG motifs in the Gr B and TPH promoters, respectively, and transactivated these two genes, indicating the involvement of +-MITF in their expression. Because TPH is the rate-limiting enzyme for serotonin synthesis, we examined the serotonin content of +/+ and mi/mi CMCs. The serotonin content was significantly smaller in mi/mi CMCs than in +/+ CMCs. The introduction of +-MITF but not of mi-MITF normalized the serotonin content in mi/mi CMCs.

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