Sterol regulatory element-binding protein 1

Sterol regulatory element-binding protein 1 (SREBP1) is a transcription factor that plays a crucial role in the regulation of lipid metabolism. It is encoded by the SREBF1 gene in humans. SREBP1 is involved in the synthesis of cholesterol, fatty acids, and triglycerides.

Function

SREBP1 is a member of the basic helix-loop-helix leucine zipper (bHLH-Zip) family of transcription factors. It binds to the sterol regulatory element (SRE) in the promoter region of target genes, activating their transcription. This process is essential for maintaining cellular lipid homeostasis.

SREBP1 exists in two isoforms, SREBP1a and SREBP1c, which are generated by alternative splicing. SREBP1c is primarily involved in the regulation of fatty acid synthesis, while SREBP1a has a broader role, influencing both fatty acid and cholesterol synthesis.

Regulation

The activity of SREBP1 is tightly regulated by sterol levels within the cell. Under low sterol conditions, SREBP1 is transported from the endoplasmic reticulum to the Golgi apparatus, where it is cleaved by site-1 and site-2 proteases. The cleaved, active form of SREBP1 then translocates to the nucleus to activate gene expression.

In contrast, high sterol levels inhibit the cleavage and activation of SREBP1, thereby reducing the expression of its target genes and decreasing lipid synthesis.

Clinical Significance

Dysregulation of SREBP1 activity is associated with various metabolic disorders, including obesity, insulin resistance, and non-alcoholic fatty liver disease (NAFLD). Overexpression of SREBP1 can lead to excessive lipid accumulation in tissues, contributing to the development of these conditions.

Research into SREBP1 and its regulatory pathways is ongoing, with the aim of developing therapeutic strategies to modulate its activity in metabolic diseases.

See Also

• Sterol regulatory element-binding protein 2
• Lipid metabolism
• Transcription factor

External Links

• [GeneCards: SREBF1](https://www.genecards.org/cgi-bin/carddisp.pl?gene=SREBF1)
• [UniProt: P36956](https://www.uniprot.org/uniprot/P36956)

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