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Cleavage Site for Sterol-regulated Protease Localized to a Leu-Ser Bond in the Lumenal Loop of Sterol Regulatory Element-binding Protein-2
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When SREBP-2 reaches the Golgi, S1P and S2P sequentially modify SREBP-2 to convert it to active nuclear SREBP-2.
“When SREBP-2 reaches the Golgi, two proteases, site 1 protease (S1P) and site 2 protease (S2P), sequentially modify SREBP-2 to convert it to its active form, designated nuclear SREBP-2 (nSREBP-2)71–73.”
From Pathways and Molecular Mechanisms Governing LDL Receptor Regulation (2025) · cites this paper as [71]
The copy’s Abstract describes Site-1 cleavage followed by Site-2 cleavage and the appearance of an SREBP-2 fragment in nuclear extracts. It does not support the Golgi location: the authors explicitly say they do not yet know where Site-1 cleavage occurs. (LLM, conf=0.90)
Experimental — accuracy not yet measuredIn the Golgi, SREBP is proteolytically activated through sequential cleavage by S1P and S2P (MBTPS1 and MBTPS2), releasing the transcriptionally active N-terminal domain.
“In the Golgi, SREBP is proteolytically activated through sequential cleavage by the proteases S1P and S2P16,17 (encoded by MBTPS1 and MBTPS2), which release the transcriptionally active N-terminal domain of SREBP.”
From Haploid genetic screens identify SPRING/C12ORF49 as a determinant of SREBP signaling and cholesterol metabolism (2020) · cites this paper as [16]
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Brown, M. S., & Goldstein, J. L. (1997) · Cell · doi:10.1016/s0092-8674(00)80213-5 · Cited by 3,834
Self-citationER Stress Induces Cleavage of Membrane-Bound ATF6 by the Same Proteases that Process SREBPs
Ye, J., Rawson, R. B., Komuro, R., Chen, X., Davé, U. P., Prywes, R., Brown, M. S., & Goldstein, J. L. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)00133-7 · Cited by 1,871
Self-citationRegulation of Sterol Synthesis in Eukaryotes
Espenshade, P. J., & Hughes, A. L. (2007) · Annual Review of Genetics · doi:10.1146/annurev.genet.41.110306.130315 · Cited by 593
Unsaturated Fatty Acids Down-regulate SREBP Isoforms 1a and 1c by Two Mechanisms in HEK-293 Cells
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Self-citationThe SREBP Pathway in Drosophila
Seegmiller, A. C., Dobrosotskaya, I., Goldstein, J. L., Ho, Y. K., Brown, M. S., & Rawson, R. B. (2002) · Developmental Cell · doi:10.1016/s1534-5807(01)00119-8 · Cited by 194
Self-citationCholesterol: From Feeding to Gene Regulation
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Loregger, A., Raaben, M., Nieuwenhuis, J., Tan, J. M. E., Jae, L. T., van den Hengel, L. G., Hendrix, S., van den Berg, M., Scheij, S., Song, J.-Y., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-14811-1 · Cited by 51
Pathways and Molecular Mechanisms Governing LDL Receptor Regulation
Schmidt, H. M., Jarrett, K. E., de Aguiar Vallim, T. Q., & Tarling, E. J. (2025) · Circulation Research · doi:10.1161/circresaha.124.323578 · Cited by 33
Metadata
- Authors
- Duncan, E. A., Brown, M. S., Goldstein, J. L., & Sakai, J.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1997-05
- Volume
- 272
- Issue
- 19
- Pages
- 12778-12785
- ISSN
- 0021-9258
- Cited by
- 158
- References
- 0
- Language
- en
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