Biology:LIN28B

From HandWiki
Short description: Protein-coding gene in the species Homo sapiens

A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example


Lin-28 homolog B is a protein that in humans is encoded by the LIN28B gene.[1] Lin28 is a gene found in both invertebrates and vertebrates, from worms to humans, where it regulates the timing of development from fertilization to adulthood.[2][3][4]

Evolution

Lin28B can be traced to a mutational event that occurred around 300 million years ago during which a large section of a heterochronic gene, Lin28, now referred to as Lin28A, was duplicated resulting in the appearance of a paralog, Lin28B.[2][3][4]

Structure

The protein encoded by this gene belongs to the lin-28 family, which is characterized by the presence of a cold-shock domain and a pair of CCHC zinc finger domains.

Tissue distribution

This gene is highly expressed in testis, fetal liver, placenta, and in primary human tumors and cancer cell lines.

Function

LIN28B is an evolutionarily conserved RNA-binding protein primarily known for its role in regulating the maturation of let-7 microRNAs, which are important for cell differentiation and development. During embryogenesis and in stem cells, LIN28B blocks differentiation and promotes cell proliferation by inhibiting let-7 biogenesis, thereby preventing the accumulation of these tumor-suppressive miRNAs. Mechanistically, the N-terminal cold-shock domain (CSD) and the C-terminal zinc-knuckle domain (ZKD) of LIN28B allow for stepwise binding to immature let-7 pre-miRNAs, triggering their remodeling and subsequent uridylation and degradation, effectively silencing their functions.[5][6][7]

developmental timing, pluripotency, and tumorigenesis, chiefly by controlling miRNA biogenesis and acting as an RNA-binding protein, but it also possesses let-7–independent roles in direct gene regulation and cellular metabolism.[6]

Clinical significance

It is negatively regulated by microRNAs that target sites in the 3' UTR, and overexpression of this gene in primary tumors is linked to the repression of let-7 family of microRNAs and derepression of let-7 targets, which facilitates cellular transformation.

Even minor changes in Lin28 are known to alter the timing of developmental stages and thereby affect all features that emerge during those stages.[2][3] The duplication shifted the developmental clock backward, such that mammals carrying both Lin28A and Lin28B gave birth earlier in gestation.[8][9] As a result, mammalian offspring were born less developed, requiring greater maternal investment. This innovation marked the appearance of mammals and accounts for two of their distinguishing features compared to reptiles and amphibians: altricial young and increased maternal bonding.[10]

References

  1. ↑ "Entrez Gene: Lin-28 homolog B". https://www.ncbi.nlm.nih.gov/gene/389421. Retrieved 2016-03-06. 
  2. ↑ 2.0 2.1 2.2 "Exploring Lin28 proteins: Unravelling structure and functions with emphasis on nervous system malignancies". Life Sciences 335. December 2023. doi:10.1016/j.lfs.2023.122275. PMID 37984514. 
  3. ↑ 3.0 3.1 3.2 "The role of Lin28A and Lin28B in cancer beyond Let-7". FEBS Letters 598 (24): 2963–2979. December 2024. doi:10.1002/1873-3468.15004. PMID 39152528. 
  4. ↑ 4.0 4.1 "Structure, expression, and mapping of two nodule-specific genes identified by mining public soybean EST databases". Gene 383: 71–80. November 2006. doi:10.1016/j.gene.2006.07.015. PMID 16973305. 
  5. ↑ "RNA-binding protein LIN28B inhibits apoptosis through regulation of the AKT2/FOXO3A/BIM axis in ovarian cancer cells". Signal Transduction and Targeted Therapy 3. 2018. doi:10.1038/s41392-018-0026-5. PMID 30174831. 
  6. ↑ 6.0 6.1 "The role of LIN28B in tumor progression and metastasis in solid tumor entities". Oncology Research 31 (2): 101–115. 2023. doi:10.32604/or.2023.028105. PMID 37304235. 
  7. ↑ "Regulation of HSC development and function by Lin28b". Frontiers in Cell and Developmental Biology 13. 2025. doi:10.3389/fcell.2025.1555877. PMID 40143971. 
  8. ↑ "Early ontogeny of locomotor behaviour: a comparison between altricial and precocial animals". Brain Research Bulletin 53 (5): 719–726. November 2000. doi:10.1016/s0361-9230(00)00404-4. PMID 11165806. 
  9. ↑ "Developmental Differences in Neocortex Neurogenesis and Maturation Between the Altricial Dwarf Rabbit and Precocial Guinea Pig". Frontiers in Neuroanatomy 15. 2021. doi:10.3389/fnana.2021.678385. PMID 34135738. 
  10. ↑ "The importance of the altricial - precocial spectrum for social complexity in mammals and birds - a review". Frontiers in Zoology 14. 2017. doi:10.1186/s12983-016-0185-6. PMID 28115975. 

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.



Retrieved from "https://handwiki.org/wiki/index.php?title=Biology:LIN28B&oldid=4052590"