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Second-site Cleavage in Sterol Regulatory Element-binding Protein Occurs at Transmembrane Junction as Determined by Cysteine Panning
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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 [72]
The Abstract describes sequential Site-1 and Site-2 cleavages that release an SREBP fragment, which travels to the nucleus and activates transcription. The Results also show Site-1 cleavage followed by S2P-dependent Site-2 cleavage in SREBP-2. Our copy does not place this processing in the Golgi or explicitly identify the Site-1 protease as S1P. (LLM, conf=0.88)
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 [17]
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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
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Espenshade, P. J., & Hughes, A. L. (2007) · Annual Review of Genetics · doi:10.1146/annurev.genet.41.110306.130315 · Cited by 593
The 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
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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
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Metadata
- Authors
- Duncan, E. A., Davé, U. P., Sakai, J., Goldstein, J. L., & Brown, M. S.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1998-07
- Volume
- 273
- Issue
- 28
- Pages
- 17801-17809
- ISSN
- 0021-9258
- Cited by
- 135
- References
- 0
- Language
- en
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