Cancer associated mutations in Sec61γ alter the permeability of the ER translocase
Translocation of secretory and integral membrane proteins across or into the ER membrane occurs via the Sec61 complex, a heterotrimeric protein complex possessing two essential sub-units, Sec61p/Sec61a and Sss1p/Sec61γ and the non-essential Sbh1p/Sec61β subunit. In addition to forming a protein cond...
| Main Authors: | , , , , , |
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| Format: | Journal Article |
| Language: | English |
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PUBLIC LIBRARY SCIENCE
2021
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| Subjects: | |
| Online Access: | http://hdl.handle.net/20.500.11937/96048 |
| _version_ | 1848766082704211968 |
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| author | Witham, Christopher M. Paxman, Aleshanee L. Baklous, Lamprini Steuart, Robert F.L. Schulz, B.L. Mousley, Carl J. |
| author_facet | Witham, Christopher M. Paxman, Aleshanee L. Baklous, Lamprini Steuart, Robert F.L. Schulz, B.L. Mousley, Carl J. |
| author_sort | Witham, Christopher M. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Translocation of secretory and integral membrane proteins across or into the ER membrane occurs via the Sec61 complex, a heterotrimeric protein complex possessing two essential sub-units, Sec61p/Sec61a and Sss1p/Sec61γ and the non-essential Sbh1p/Sec61β subunit. In addition to forming a protein conducting channel, the Sec61 complex maintains the ER permeability barrier, preventing flow of molecules and ions. Loss of Sec61 integrity is detrimental and implicated in the progression of disease. The Sss1p/Sec61? C-terminus is juxtaposed to the key gating module of Sec61p/Sec61a and is important for gating the translocon. Inspection of the cancer genome database identifies six mutations in highly conserved amino acids of Sec61γ/Sss1p. We identify that five out of the six mutations identified affect gating of the ER translocon, albeit with varying strength. Together, we find that mutations in Sec61γ that arise in malignant cells result in altered translocon gating dynamics, this offers the potential for the translocon to represent a target in co-therapy for cancer treatment. |
| first_indexed | 2025-11-14T11:45:30Z |
| format | Journal Article |
| id | curtin-20.500.11937-96048 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T11:45:30Z |
| publishDate | 2021 |
| publisher | PUBLIC LIBRARY SCIENCE |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-960482024-11-13T07:19:23Z Cancer associated mutations in Sec61γ alter the permeability of the ER translocase Witham, Christopher M. Paxman, Aleshanee L. Baklous, Lamprini Steuart, Robert F.L. Schulz, B.L. Mousley, Carl J. Science & Technology Life Sciences & Biomedicine Genetics & Heredity SIGNAL RECOGNITION PROTEIN ENDOPLASMIC-RETICULUM MEMBRANE-PROTEIN BOUND RIBOSOMES CROSS-LINKING CA2+ YEAST PEPTIDE CHANNEL SSS1P Amino Acid Sequence Biological Transport Cell Membrane Permeability Endoplasmic Reticulum Membrane Proteins Membrane Transport Proteins Mutation Neoplasms Protein Transport SEC Translocation Channels Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins Endoplasmic Reticulum Saccharomyces cerevisiae Neoplasms Membrane Transport Proteins Saccharomyces cerevisiae Proteins Membrane Proteins Cell Membrane Permeability Amino Acid Sequence Biological Transport Protein Transport Mutation SEC Translocation Channels Translocation of secretory and integral membrane proteins across or into the ER membrane occurs via the Sec61 complex, a heterotrimeric protein complex possessing two essential sub-units, Sec61p/Sec61a and Sss1p/Sec61γ and the non-essential Sbh1p/Sec61β subunit. In addition to forming a protein conducting channel, the Sec61 complex maintains the ER permeability barrier, preventing flow of molecules and ions. Loss of Sec61 integrity is detrimental and implicated in the progression of disease. The Sss1p/Sec61? C-terminus is juxtaposed to the key gating module of Sec61p/Sec61a and is important for gating the translocon. Inspection of the cancer genome database identifies six mutations in highly conserved amino acids of Sec61γ/Sss1p. We identify that five out of the six mutations identified affect gating of the ER translocon, albeit with varying strength. Together, we find that mutations in Sec61γ that arise in malignant cells result in altered translocon gating dynamics, this offers the potential for the translocon to represent a target in co-therapy for cancer treatment. 2021 Journal Article http://hdl.handle.net/20.500.11937/96048 10.1371/journal.pgen.1009780 English http://creativecommons.org/licenses/by/4.0/ PUBLIC LIBRARY SCIENCE fulltext |
| spellingShingle | Science & Technology Life Sciences & Biomedicine Genetics & Heredity SIGNAL RECOGNITION PROTEIN ENDOPLASMIC-RETICULUM MEMBRANE-PROTEIN BOUND RIBOSOMES CROSS-LINKING CA2+ YEAST PEPTIDE CHANNEL SSS1P Amino Acid Sequence Biological Transport Cell Membrane Permeability Endoplasmic Reticulum Membrane Proteins Membrane Transport Proteins Mutation Neoplasms Protein Transport SEC Translocation Channels Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins Endoplasmic Reticulum Saccharomyces cerevisiae Neoplasms Membrane Transport Proteins Saccharomyces cerevisiae Proteins Membrane Proteins Cell Membrane Permeability Amino Acid Sequence Biological Transport Protein Transport Mutation SEC Translocation Channels Witham, Christopher M. Paxman, Aleshanee L. Baklous, Lamprini Steuart, Robert F.L. Schulz, B.L. Mousley, Carl J. Cancer associated mutations in Sec61γ alter the permeability of the ER translocase |
| title | Cancer associated mutations in Sec61γ alter the permeability of the ER translocase |
| title_full | Cancer associated mutations in Sec61γ alter the permeability of the ER translocase |
| title_fullStr | Cancer associated mutations in Sec61γ alter the permeability of the ER translocase |
| title_full_unstemmed | Cancer associated mutations in Sec61γ alter the permeability of the ER translocase |
| title_short | Cancer associated mutations in Sec61γ alter the permeability of the ER translocase |
| title_sort | cancer associated mutations in sec61γ alter the permeability of the er translocase |
| topic | Science & Technology Life Sciences & Biomedicine Genetics & Heredity SIGNAL RECOGNITION PROTEIN ENDOPLASMIC-RETICULUM MEMBRANE-PROTEIN BOUND RIBOSOMES CROSS-LINKING CA2+ YEAST PEPTIDE CHANNEL SSS1P Amino Acid Sequence Biological Transport Cell Membrane Permeability Endoplasmic Reticulum Membrane Proteins Membrane Transport Proteins Mutation Neoplasms Protein Transport SEC Translocation Channels Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins Endoplasmic Reticulum Saccharomyces cerevisiae Neoplasms Membrane Transport Proteins Saccharomyces cerevisiae Proteins Membrane Proteins Cell Membrane Permeability Amino Acid Sequence Biological Transport Protein Transport Mutation SEC Translocation Channels |
| url | http://hdl.handle.net/20.500.11937/96048 |