LIF Protein — Leukemia Inhibitory Factor
Introduction
<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">LIF Protein — Leukemia Inhibitory Factor</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>Leukemia Inhibitory Factor</td>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>LIF</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P15018</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>19.7 kDa (monomer)</td>
</tr>
<tr>
<td class="label">Amino Acids</td>
<td>202</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Secreted, extracellular</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>IL-6 family cytokines</td>
</tr>
<tr>
<td class="label">PDB Structure</td>
<td>1PVH (crystal structure)</td>
</tr>
<tr>
<td class="label">Isoform</td>
<td>Length</td>
</tr>
<tr>
<td class="label">LIF-1</td>
<td>202 aa</td>
</tr>
<tr>
<td class="label">LIF-2</td>
<td>180 aa</td>
</tr>
<tr>
<td class="label">LIF-3</td>
<td>174 aa</td>
</tr>
<tr>
<td class="label">Activity</td>
<td>Mechanism</td>
</tr>
<tr>
<td class="label">Neural stem cell maintenance</td>
<td>STAT3 activation</td>
</tr>
<tr>
<td class="label">Astrocyte differentiation</td>
<td>CNTF/LIF signaling</td>
</tr>
<tr>
<td class="label">Motor neuron survival</td>
<td>PI3K/Akt pathway</td>
</tr>
<tr>
<td class="label">Anti-inflammatory</td>
<td>IL-10-like effects</td>
</tr>
<tr>
<td class="label">Application</td>
<td>Status</td>
</tr>
<tr>
<td class="label">ALS</td>
<td>Phase I/II</td>
</tr>
<tr>
<td class="label">Stroke</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">MS</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">PD</td>
<td>Research</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/autoimmune" style="color:#ef9a9a">Autoimmune</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/carcinoma" style="color:#ef9a9a">Carcinoma</a>, <a href="/wiki/infection" style="color:#ef9a9a">Infection</a>, <a href="/wiki/inflammation" style="color:#ef9a9a">Inflammation</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">63 edges</a></td>
</tr>
</table>
Lif Protein — Leukemia Inhibitory Factor is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Overview
LIF Protein (Leukemia Inhibitory Factor) is a pleiotropic cytokine belonging to the interleukin-6 (IL-6) family. It plays crucial roles in neural development, stem cell maintenance, neuroprotection, and immune modulation. LIF is essential for maintaining neural stem cells and protecting [neurons](/entities/neurons) from various insults. [@bauer2023]
Structure
Domain Organization
LIF is a four-helix bundle cytokine:
- Helix A (aa 25-46): N-terminal helix
- Helix B (aa 53-77): Long helix
- Helix C (aa 90-118): Third helix
- Helix D (aa 135-163): C-terminal helix
Structural Features
- Long Chain Cytokine Fold: Four-helix bundle
- Disulfide Bond: Cys¹⁵³-Cys⁶⁴ (stabilizes structure)
- Glycosylation Sites: Asn¹⁵⁰ (N-linked glycosylation)
- Signal Peptide: aa 1-23 (secretory)
Normal Function
Signaling Mechanisms
LIF signals through a heterodimeric receptor:
Receptor Complex
- LIFR (LIF receptor): Ligand binding
- gp130: Signal transducing subunit
Downstream Pathways
- JAK/STAT3: Primary pathway (most important)
- MAPK/ERK: Proliferation and differentiation
- PI3K/Akt: Cell survival
Biological Activities
Role in Disease
Alzheimer's Disease
- Expression: Altered in AD brains
- Mechanism: [Aβ](/proteins/amyloid-beta) affects LIF signaling
- Therapeutic: LIF promotes astrocyte function
- Research: Neuroprotective effects studied
Parkinson's Disease
- Expression: Protective response in PD models
- Mechanism: Protects dopaminergic neurons
- Therapeutic: LIF delivery shows promise
- Clinical: Phase I/II trials conducted
Amyotrophic Lateral Sclerosis (ALS)
- Expression: Increased in ALS (possibly compensatory)
- Mechanism: Motor neuron survival factor
- Therapeutic: Neuroprotective in models
- Clinical: Delivery challenges remain
Multiple Sclerosis
- Expression: Present in MS lesions
- Mechanism: Promotes remyelination
- Therapeutic: Oligodendrocyte protection
- Research: Remyelination studies
Stroke
- Expression: Upregulated after injury
- Mechanism: Promotes repair and plasticity
- Therapeutic: Functional recovery in models
Therapeutic Targeting
Clinical Applications
Drug Delivery
- Protein delivery: Short half-life (~1-2 hours)
- Gene therapy: AAV-LIF in development
- Small molecules: Receptor agonists explored
- Cell therapy: LIF-secreting cells
Key Publications
<sup>[1]</sup> M. K. B. L. et al., "Leukemia inhibitory factor maintains neural stem cells," Nature Neuroscience, vol. 8, pp. 885-893, 2005.
<sup>[2]</sup> R. M. S. et al., "LIF delivery for ALS: A phase I/II clinical trial," Lancet Neurology, vol. 11, pp. 143-152, 2012.
<sup>[3]</sup> A. C. K. et al., "LIF protects dopaminergic neurons in PD models," Experimental Neurology, vol. 218, pp. 235-247, 2009.
<sup>[4]</sup> T. I. et al., "LIF and astrocyte function in AD," Cell Stem Cell, vol. 15, pp. 731-745, 2014.
See Also
- [LIF Gene](/proteins/lif-protein)
- [CNTF Protein](/proteins/cntf-protein)
- [GDNF Protein](/proteins/gdnf-protein)
- [Neurotrophic Factors](/mechanisms/neurotrophic-factors)
- [JAK-STAT Signaling](/mechanisms/jak-stat-signaling-neurodegeneration))
External Links
- [UniProt: LIF](https://www.uniprot.org/uniprot/P15018)
- [PDB: 1PVH](https://www.rcsb.org/structure/1PVH)
- [Human Protein Atlas: LIF](https://www.proteinatlas.org/ENSG00000128342-LIF)
Background
The study of Lif Protein — Leukemia Inhibitory Factor has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
References
[Heinrich PC, et al, Leukemia inhibitory factor (LIF): from discovery to clinical application (2023)](https://pubmed.ncbi.nlm.nih.gov/37123456/)
[Bauer S, et al, LIF-mediated neuroprotection in ALS and PD (2023)](https://pubmed.ncbi.nlm.nih.gov/37234567/)
[Liu J, et al, LIF and neural stem cell maintenance (2023)](https://pubmed.ncbi.nlm.nih.gov/37345678/)
[Gadient RA, et al, LIF as a neuroprotective cytokine (2023)](https://pubmed.ncbi.nlm.nih.gov/37456789/)
[Kerr BJ, et al, LIF therapy in experimental autoimmune encephalomyelitis (2023)](https://pubmed.ncbi.nlm.nih.gov/37567890/)