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Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor (LATS) Biosensor
Published on: September 13, 2018
Two forms of the large tumor suppressor gene (Lats1) protein expressed in the vertebrate retina
Novrouz B Akhmedov1, Clyde K Yamashita, Dai Tran
1Jules Stein Eye Institute, UCLA School of Medicine, 100 Stein Plaza, Los Angeles, CA 90095, USA. akhmedov@jsei.ucla.edu
Abstract:
The large tumor suppressor gene (Lats1) encodes a protein kinase that is highly conserved from fly to human, and plays a crucial role in the prevention of tumor formation by controlling mitosis progression. We have found that in addition to the previously isolated 7.5 kb long form of Lats1 (Lats1L) mRNA, a less abundant, shorter, 3.4 kb primary transcript (Lats1S) also is expressed in the vertebrate retina. Compared to Lats1L, the sequence of Lats1S mRNA has a deletion of exons 6, 7, and 8 that corresponds to 792 bp of the open reading frame. Thus, 264 aa of the C-terminal region of the long transcript are missing in the Lats1S protein. The encoded truncated protein lacks four of eleven conserved kinase domains and the C-terminus. Our results suggest that the 3.4 kb transcript is a splice variant of the 7.5 kb transcript. We have found direct evidence that both the retinal 7.5 and 3.4 kb mRNAs are translated into 170 kDa and 120 kDa proteins, respectively. The expression of both isoforms in vertebrate cells raises the possibility that these Lats1 proteins may act as negative key regulators of the cell cycle, each of them performing a unique role.
Insights
Researchers discovered a shorter Lats1S mRNA variant in vertebrate retinas, alongside the known Lats1L form. This shorter transcript produces a distinct protein, suggesting unique roles for Lats1 isoforms in cell cycle regulation.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- The large tumor suppressor gene (Lats1) is a conserved protein kinase critical for preventing tumor formation by regulating mitosis.
- Previous research identified a 7.5 kb Lats1L mRNA form.
Purpose of the Study:
- To investigate the expression and potential function of alternative Lats1 mRNA transcripts in vertebrate retina.
- To characterize a newly identified shorter Lats1 transcript and its encoded protein.
Main Methods:
- RT-PCR to detect and analyze Lats1 mRNA variants.
- Sequence analysis to identify differences between Lats1L and Lats1S.
- Western blotting or similar techniques to confirm protein expression.
Main Results:
- A shorter 3.4 kb Lats1S primary transcript was identified in vertebrate retina, in addition to the 7.5 kb Lats1L mRNA.
- The Lats1S mRNA results from a deletion of exons 6, 7, and 8, leading to a truncated protein lacking key kinase domains and the C-terminus.
- Both Lats1L and Lats1S mRNAs are translated into distinct proteins (170 kDa and 120 kDa, respectively).
Conclusions:
- The 3.4 kb transcript is likely a splice variant of the 7.5 kb transcript.
- The expression of both Lats1 protein isoforms in vertebrate cells suggests they may function as negative regulators of the cell cycle, each with a unique role.
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