Table 1.
Cellular functions and locations of leaderless secretory proteins
| Protein | Extracellular function | Intracellular localization and function | References |
|---|---|---|---|
| Cytokines | |||
| IL-1α | Mediator of inflammation and immune response | Nucleus, regulation of transcription | 68, 119 (see also Ref. 66 and references therein) |
| IL-1β | Mediator of inflammation and immune response | Cytosol, function NDa | 5 (see also Ref. 66 and references therein |
| IL-18 | Mediator of inflammation and immune response | Cytosol, function ND | 66 (and references therein), 120 |
| IL-33 | Mediator of inflammation and immune response | Nucleus, function ND | 69 (see also Ref. 66 and references therein) |
| IL-37 | Inhibitor of innate immunity | Cytosol and nucleus, inhibitor of innate immunity | 70 |
| Caspase-1 | Extracellular processing of pro-IL-1? | Cytosol, IL-1β, and IL-18 convertase; mediator of secretion of other LLSPs | 119, 121 |
| FGF-1/acidic FGF | Growth, survival, and differentiating factor | Nucleus, anti-apoptotic, neurotrophic factor | 122 (and references therein) |
| FGF-2/basic FGF | Growth, survival, and differentiating factor | Nuclear, anti-apoptotic factor | 10 (see also Ref. 123 and references therein) |
| Annexin A1, A2, A4, A5 | Modulators of coagulation and anti-inflammatory mediator; soluble or bound to the outer leaflet of the plasma membrane | Cytosol: membrane trafficking and organization; nucleus: pro-apoptotic | 124 (and references therein) |
| Members of the galectin protein family | Mediator of innate immunity | Cytosol, pro-apoptotic | 7 (see also Ref. 124 and references therein) |
| Members of the S100 protein family (S100A8, S100A9) | Antimicrobial and chemotactic activities | Cytosol, EF-hand domain--containing Ca2+-binding proteins | 125 |
| MIF-1 | Pro-inflammatory mediator | Cytosol, function ND | 48, 126 |
| Endothelial monocyte--activating polypeptide (EMAP)-2 | Pro-inflammatory mediator with anti-angiogenic properties | Cytosol, protein translation (tRNA multisynthetase complex) | 127 |
| HMGB1 | Mediator of inflammation and immune response | Nucleus, transcriptional regulation, DNA replication and repair, and nucleosome assembly | 30 (see also Ref. 128 and references therein) |
| Phosphoglucose isomerase/autocrine motility factor (PGI/AMF) | Inducer of cell migration | Cytosol, glycolytic enzyme (phosphoglucose isomerase) | 129 |
| Redox enzymes | |||
| Trx | Cytokine-like inflammatory mediator, possibly through thiol-disulfide exchange | Cytosol, oxidoreductase | 9 |
| Trx reductase (TrxR) | Regeneration of oxidized Trx? | Cytosol, Trx reductase | 130 |
| Peroxiredoxin (PRDX)1, PRDX2 | Cytokine-like inflammatory mediator, possibly through peroxidation reactions | Cytosol, peroxidases | 85, 131 |
| SOD-1 | Prion-like properties, involved in familial ALS | Cytosol; converts superoxide radicals to molecular oxygen and hydrogen peroxide | 75, 132 |
| Brain proteins | |||
| APE1/Ref-1 | Cytokine-like anti-inflammatory mediator, through thiol-disulfide exchange | Nucleus, antioxidant | 49, 73 |
| CNTF | Cytokine, member of the IL-6 family; neuroprotective, anti-inflammatory | Cytosol, function ND | 72, 134 |
| Tau | Interneuronal signaling, trans-synaptic transmission | Cytosol, stabilization of microtubules | 135 (see also Ref. 33 and references therein) |
| α-Synuclein | Internalized by neurons, modulator of neuronal death | Presynaptic vesicle, functioning as modulator of synaptic vesicle mobility | 136–138 |
| Engrailed 2 | Secreted by tumor cells, modifies tumor microenvironment | Nucleus, homeodomain-containing transcription factor functioning in early development | 60, 139 |
| Others | |||
| Transglutaminase | Cross-linking enzyme with pleiotropic activity; regulates the cellular interactions with the extracellular matrix | Cytosol, nucleus, mitochondria; cross-linking enzyme with pleiotropic activity; NF-KB activator | 140, 141 |
| Insulin-degrading enzyme (IDE) | Zn2+ peptidase, amyloid peptide degradation | Cytosol, Zn2+ peptidase | 142 |
a ND, not determined.