高濃度のtRNA ((iMet) 合成は,細胞増殖と腫瘍性変異を促す可能性があります
Lynne Marshall1, Niall S Kenneth, Robert J White
1Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK.
Cell
|April 9, 2008
まとめ
増加したRNAポリメラーゼIII (polIII) 転写,特に転送RNA (tRNA) 合成の増加は,細胞増殖と腫瘍性変異を誘発する. これは,tRNA生成が腫瘍発達の重要な要因であることを示唆しています.
科学分野:
- 分子生物学は分子生物学である.
- がん研究 がん研究
- 細胞生物学 細胞生物学
背景:
- トランスフォーメーションおよび腫瘍細胞は,タンパク質合成が強化され,tRNAや5SrRNAのようなRNAポリメラーゼIII (polIII) 産物も増加しています.
- 細胞変容における規制解除されたポルIII転写の正確な役割は,まだ完全に理解されていません.
研究 の 目的:
- 上調されたポリIIIトランスクリプションが腫瘍性変異に直接寄与するかどうかを調査する.
- tRNAなどの特定のpol III製品が細胞の増殖と変容に与える影響を決定する.
主な方法:
- ポリIII特異の転写因子 Brf1.1. を発現する誘導性細胞系を生成する.
- Brf1レベルを操作して,特異的にtRNAと5SrRNAの合成を変化させる.
- 細胞増殖,腫瘍性変異,および腫瘍形成の評価 in vivo.
主要な成果:
- Brf1誘導は,tRNAと5SrRNAのレベルを上昇させ,細胞増殖と腫瘍性変異を促進しました.
- Brf1の枯渇は変換を阻害し,その重要な役割を強調した.
- 重要なポルIII産物であるtRNAの過剰発現は,マウスの増殖を刺激し,腫瘍形成を誘発するのに十分であった.
結論:
- ポリIII転写によって誘発されるtRNA合成の上昇は,細胞変容の重要な促進因子である.
- ポリIII活性やtRNA合成をターゲットにすることは,がんに対する新たな治療戦略である可能性があります.
関連する概念動画
01:33Cancer-Critical Genes I: Proto-oncogenes
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
03:03mTOR Signaling and Cancer Progression
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
02:38Mitogens and the Cell Cycle
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
01:06Induced Pluripotent Stem Cells
Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic cells are...
Somatic cells are...
02:38The Ras Gene
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Ras is a superfamily...