Identification of the endoplasmic reticulum localization sequence and <i>N</i>-glycosylation of matrix metalloproteinase 26

Zhang, Guangji; Zhang, Jinrui; Li, Xiang; Meng, Xin; Fang, Xuexun

doi:10.1039/c9ra05222d

Cited by 3 publications

(3 citation statements)

References 30 publications

(42 reference statements)

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“…MMPs are generally excreted via the endoplasmic reticulum as a result of the N-terminal secretory signal [ 1 , 21 ]. However, in HEK293 cells, about half of nascent MMP-2 is retained inside the cell due to an inefficient secretory signal sequence [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Novel Roles of MT1-MMP and MMP-2: Beyond the Extracellular Milieu

Maybee

Ink

Ali

2022

IJMS

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Matrix metalloproteinases (MMPs) are critical enzymes involved in a variety of cellular processes. MMPs are well known for their ability to degrade the extracellular matrix (ECM) and their extracellular role in cell migration. Recently, more research has been conducted on investigating novel subcellular localizations of MMPs and their intracellular roles at their respective locations. In this review article, we focus on the subcellular localization and novel intracellular roles of two closely related MMPs: membrane-type-1 matrix metalloproteinase (MT1-MMP) and matrix metalloproteinase-2 (MMP-2). Although MT1-MMP is commonly known to localize on the cell surface, the protease also localizes to the cytoplasm, caveolae, Golgi, cytoskeleton, centrosome, and nucleus. At these subcellular locations, MT1-MMP functions in cell migration, macrophage metabolism, invadopodia development, spindle formation and gene expression, respectively. Similar to MT1-MMP, MMP-2 localizes to the caveolae, mitochondria, cytoskeleton, nucleus and nucleolus and functions in calcium regulation, contractile dysfunction, gene expression and ribosomal RNA transcription. Our particular interest lies in the roles MMP-2 and MT1-MMP serve within the nucleus, as they may provide critical insights into cancer epigenetics and tumor migration and invasion. We suggest that targeting nuclear MT1-MMP or MMP-2 to reduce or halt cell proliferation and migration may lead to the development of new therapies for cancer and other diseases.

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Section: Introductionmentioning

confidence: 99%

Novel Roles of MT1-MMP and MMP-2: Beyond the Extracellular Milieu

Maybee

Ink

Ali

2022

IJMS

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“…While the misfolded protein produced by a truncated set of genes will be retained in the ER and processed for ER-related degradation [ 51 ], the deletion of rfa genes may lead to the further interference of the membrane’s subsequent function [ 50 ]. Moreover, glycosylation deficiencies in the LPS protein production also disrupt protein localization in ER, which affects the functional membrane of protein [ 52 ]. In addition, the KEGG prediction showed high expression of PFKA, GAPA, and PYKA in E. coli by rfaL gene knockout ( Figure 7 b).…”

Section: Discussionmentioning

confidence: 99%

Proteomic Profiling of Outer Membrane Vesicles Released by Escherichia coli LPS Mutants Defective in Heptose Biosynthesis

Chiu

Yin

Lee

et al. 2022

JPM

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Escherichia coli releases outer membrane vesicles (OMVs) into the extracellular environment. OMVs, which contain the outer membrane protein, lipopolysaccharides (LPS), and genetic material, play an important role in immune response modulation. An isobaric tag for relative and absolute quantitation (iTRAQ) analysis was used to investigate OMV constituent proteins and their functions in burn trauma. OMV sizes ranged from 50 to 200 nm. Proteomics and Gene Ontology analysis revealed that ΔrfaC and ΔrfaG were likely involved in the upregulation of the structural constituent of ribosomes for the outer membrane and of proteins involved in protein binding and OMV synthesis. ΔrfaL was likely implicated in the downregulation of the structural constituent of the ribosome, translation, and cytosolic large ribosomal subunit. Kyoto Encyclopedia of Genes and Genomes analysis indicated that ΔrfaC and ΔrfaG downregulated ACP, ACEF, and ADHE genes; ΔrfaL upregulated ACP, ACEF, and ADHE genes. Heat map analysis demonstrated upregulation of galF, clpX, accA, fabB, and grpE and downregulation of pspA, ydiY, rpsT, and rpmB. These results suggest that RfaC, RfaG, and RfaL proteins were involved in outer membrane and LPS synthesis. Therefore, direct contact between wounds and LPS may lead to apoptosis, reduction in local cell proliferation, and delayed wound healing.

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“…Generally, misfolded proteins are retained in the ER and processed for ER-associated degradation ( Araki and Nagata, 2012 ). Glycosylation deficiencies can disrupt protein localization in the ER ( Zhang et al, 2019 ). In this study, we identified three N-glycosylation sites in the full-length PDGF-C protein that include Asn25, Asn55, and Asn254.…”

Section: Discussionmentioning

confidence: 99%

Glycosylation at Asn254 Is Required for the Activation of the PDGF-C Protein

Zhang

Chen

et al. 2021

Front. Mol. Biosci.

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Platelet-derived growth factor C (PDGF-C) is a member of the PDGF/VEGF (vascular endothelial growth factor) family, which includes proteins that are well known for their mitogenic effects on multiple cell types. Glycosylation is one of the most important forms of posttranslational modification that has a significant impact on secreted and membrane proteins. Glycosylation has many well-characterized roles in facilitating protein processing and contributes to appropriate folding, conformation, distribution, and stability of proteins that are synthesized intracellularly in the endoplasmic reticulum (ER) and Golgi apparatus. Although the general process and functions of glycosylation are well documented, there are most likely others yet to be discovered, as the glycosylation of many potential substrates has not been characterized. In this study, we report that the PDGF-C protein is glycosylated at three sites, including Asn25, Asn55, and Asn254. However, we found that mutations at any of these sites do not affect the protein expression or secretion. Similarly, disruption of PDGF-C glycosylation had no impact on its progression through the ER and Golgi apparatus. However, the introduction of a mutation at Asn254 (N254 A) prevents the activation of full-length PDGF-C and its capacity for signaling via the PDGF receptor. Our findings reveal that glycosylation affects PDGF-C activation rather than the protein synthesis or processing. This study characterizes a crucial modification of the PDGF-C protein, and may shed new light on the process and function of glycosylation.

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Identification of the endoplasmic reticulum localization sequence and N-glycosylation of matrix metalloproteinase 26

Abstract: Matrix metalloproteinase 26 (MMP-26), also called endometase and matrilysin-2, belongs to the MMP superfamily.

Cited by 3 publications

References 30 publications

Novel Roles of MT1-MMP and MMP-2: Beyond the Extracellular Milieu

Novel Roles of MT1-MMP and MMP-2: Beyond the Extracellular Milieu

Proteomic Profiling of Outer Membrane Vesicles Released by Escherichia coli LPS Mutants Defective in Heptose Biosynthesis

Glycosylation at Asn254 Is Required for the Activation of the PDGF-C Protein

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