LIN28B
Domain
The tandem zinc fingers, also referred as zinc knuckle domain (ZKD), mediate specific binding to the GGAG/GGUG motif while the CSD shows only limited pyrimidine-rich sequence specificity. Both domains bind single-stranded nucleic acids.
Function
Suppressor of microRNA (miRNA) biogenesis, including that of let-7 and possibly of miR107, miR-143 and miR-200c. Binds primary let-7 transcripts (pri-let-7), including pri-let-7g and pri-let-7a-1, and sequester them in the nucleolus, away from the microprocessor complex, hence preventing their processing into mature miRNA (PubMed:22118463). Does not act on pri-miR21 (PubMed:22118463). The repression of let-7 expression is required for normal development and contributes to maintain the pluripotent state of embryonic stem cells by preventing let-7-mediated differentiation. When overexpressed, recruits ZCCHC11/TUT4 uridylyltransferase to pre-let-7 transcripts, leading to their terminal uridylation and degradation (PubMed:19703396). This activity might not be relevant in vivo, as LIN28B-mediated inhibition of let-7 miRNA maturation appears to be ZCCHC11-independent (PubMed:22118463). Interaction with target pre-miRNAs occurs via an 5'-GGAG-3' motif in the pre-miRNA terminal loop. Mediates MYC-induced let-7 repression (By similarity). When overexpressed, isoform 1 stimulates growth of the breast adenocarcinoma cell line MCF-7. Isoform 2 has no effect on cell growth.
Sequence Similarities
Belongs to the lin-28 family.
Tissue Specificity
Expressed at high levels in the placenta and, at mucher lower, in testis and fetal liver (PubMed:16971064). Isoform 1 is only detected in placenta and in moderately and poorly differentiated hepatocellular carcinoma cells (at protein level). Isoform 2 is detected in fetal liver, non-tumor liver tissues, as well as well-differentiated tumor tissues (at protein level). Tends to be up-regulated in triple-negative (ER-,PR-,HER2-) breast tumors, as well as in liver, ovarian, and thyroid carcinomas (PubMed:22118463).
Cellular localization
- Nucleus
- Nucleus
- Nucleolus
- Cytoplasm
- Predominantly nucleolar (PubMed:22118463). In Huh7 cells, predominantly cytoplasmic, with only a subset of cells exhibiting strong nuclear staining; however, the specificity of the polyclonal antibody used in these experiments has not been not documented (PubMed:16971064).
Alternative names
CSDD2, LIN28B, Protein lin-28 homolog B, Lin-28B