Two isoforms of tissue transglutaminase mediate opposing cellular fates
Two isoforms of tissue transglutaminase mediate opposing cellular fates
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DOI：
10.1073/pnas.0604844103
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发表时间：
2006-12-05
影响因子：
11.1
通讯作者：
Cerione, Richard A.
中科院分区：
文献类型：
--
作者：
Antonyak, Marc A.;Jansen, Jaclyn M.;Cerione, Richard A.
相反的细胞反应通常由不同的基因组调节。然而，组织转谷氨酰胺酶（TGase）提供了一个有趣的单基因产物的例子，它既涉及提供对细胞损伤的保护，也涉及促进细胞死亡。在这里，我们通过证明TGase的不同转录本对细胞活力的不同影响，阐明了这些相互冲突的活性是如何表现出来的。我们表明，尽管全长TGase蛋白对细胞死亡信号提供了强有力的保护，但在3'端被截断的较短版本的TGase，因此被称为TGase-short (TGase- s)，具有细胞毒性。TGase-S的凋亡活性并不依赖于它的转酰胺活性，因为催化该反应所必需的半胱氨酸残基的突变不会损害TGase-S诱导细胞死亡的能力。有趣的是，在细胞死亡之前，TGase-S在细胞中经历了不适当的低聚物形成，这提示了该蛋白凋亡作用的新机制。
Opposing cellular responses are typically regulated by distinct sets of genes. However, tissue transglutaminase (TGase) provides an interesting example of a single gene product that has been implicated both in affording protection against cellular insults as well as in promoting cell death. Here, we shed some light on how these conflicting activities might be manifested by demonstrating that alternative transcripts of TGase differentially affect cell viability. We show that although the full-length TGase protein affords strong protection against cell death signals, a shorter version of TGase that is truncated at the 3' end, and thus called TGase-short (TGase-S), is cytotoxic. The apoptotic activity of TGase-S is not dependent on its transamidation activity because the mutation of a cysteine residue that is essential for catalyzing this reaction does not compromise the ability of TGase-S to induce cell death. Intriguingly, TGase-S undergoes inappropriate oligomer formation in cells before cell death, suggesting a novel mechanism for the apoptotic effects of this protein.