Caspase-2 short isoform interacts with membrane-associated cytoskeleton proteins to inhibit apoptosis.

Caspase-2 (casp-2) is the most conserved caspase across species, and is one of the initiator caspases activated by various stimuli. The casp-2 gene produces several alternative splicing isoforms. It is believed that the long isoform, casp-2L, promotes apoptosis, whereas the short isoform, casp-2S, i...

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Autores principales:	Chunhua Han, Ran Zhao, John Kroger, Meihua Qu, Altaf A Wani, Qi-En Wang
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5a3238de228f4574addf29b94dcb9bbf
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spelling	oai:doaj.org-article:5a3238de228f4574addf29b94dcb9bbf2021-11-18T07:39:17ZCaspase-2 short isoform interacts with membrane-associated cytoskeleton proteins to inhibit apoptosis.1932-620310.1371/journal.pone.0067033https://doaj.org/article/5a3238de228f4574addf29b94dcb9bbf2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23840868/?tool=EBIhttps://doaj.org/toc/1932-6203Caspase-2 (casp-2) is the most conserved caspase across species, and is one of the initiator caspases activated by various stimuli. The casp-2 gene produces several alternative splicing isoforms. It is believed that the long isoform, casp-2L, promotes apoptosis, whereas the short isoform, casp-2S, inhibits apoptosis. The actual effect of casp-2S on apoptosis is still controversial, however, and the underlying mechanism for casp-2S-mediated apoptosis inhibition is unclear. Here, we analyzed the effects of casp-2S on DNA damage induced apoptosis through "gain-of-function" and "loss-of-function" strategies in ovarian cancer cell lines. We clearly demonstrated that the over-expression of casp-2S inhibited, and the knockdown of casp-2S promoted, the cisplatin-induced apoptosis of ovarian cancer cells. To explore the mechanism by which casp-2S mediates apoptosis inhibition, we analyzed the proteins which interact with casp-2S in cells by using immunoprecipitation (IP) and mass spectrometry. We have identified two cytoskeleton proteins, Fodrin and α-Actinin 4, which interact with FLAG-tagged casp-2S in HeLa cells and confirmed this interaction through reciprocal IP. We further demonstrated that casp-2S (i) is responsible for inhibiting DNA damage-induced cytoplasmic Fodrin cleavage independent of cellular p53 status, and (ii) prevents cisplatin-induced membrane blebbing. Taken together, our data suggests that casp-2S affects cellular apoptosis through its interaction with membrane-associated cytoskeletal Fodrin protein.Chunhua HanRan ZhaoJohn KrogerMeihua QuAltaf A WaniQi-En WangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 7, p e67033 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chunhua Han Ran Zhao John Kroger Meihua Qu Altaf A Wani Qi-En Wang Caspase-2 short isoform interacts with membrane-associated cytoskeleton proteins to inhibit apoptosis.
description	Caspase-2 (casp-2) is the most conserved caspase across species, and is one of the initiator caspases activated by various stimuli. The casp-2 gene produces several alternative splicing isoforms. It is believed that the long isoform, casp-2L, promotes apoptosis, whereas the short isoform, casp-2S, inhibits apoptosis. The actual effect of casp-2S on apoptosis is still controversial, however, and the underlying mechanism for casp-2S-mediated apoptosis inhibition is unclear. Here, we analyzed the effects of casp-2S on DNA damage induced apoptosis through "gain-of-function" and "loss-of-function" strategies in ovarian cancer cell lines. We clearly demonstrated that the over-expression of casp-2S inhibited, and the knockdown of casp-2S promoted, the cisplatin-induced apoptosis of ovarian cancer cells. To explore the mechanism by which casp-2S mediates apoptosis inhibition, we analyzed the proteins which interact with casp-2S in cells by using immunoprecipitation (IP) and mass spectrometry. We have identified two cytoskeleton proteins, Fodrin and α-Actinin 4, which interact with FLAG-tagged casp-2S in HeLa cells and confirmed this interaction through reciprocal IP. We further demonstrated that casp-2S (i) is responsible for inhibiting DNA damage-induced cytoplasmic Fodrin cleavage independent of cellular p53 status, and (ii) prevents cisplatin-induced membrane blebbing. Taken together, our data suggests that casp-2S affects cellular apoptosis through its interaction with membrane-associated cytoskeletal Fodrin protein.
format	article
author	Chunhua Han Ran Zhao John Kroger Meihua Qu Altaf A Wani Qi-En Wang
author_facet	Chunhua Han Ran Zhao John Kroger Meihua Qu Altaf A Wani Qi-En Wang
author_sort	Chunhua Han
title	Caspase-2 short isoform interacts with membrane-associated cytoskeleton proteins to inhibit apoptosis.
title_short	Caspase-2 short isoform interacts with membrane-associated cytoskeleton proteins to inhibit apoptosis.
title_full	Caspase-2 short isoform interacts with membrane-associated cytoskeleton proteins to inhibit apoptosis.
title_fullStr	Caspase-2 short isoform interacts with membrane-associated cytoskeleton proteins to inhibit apoptosis.
title_full_unstemmed	Caspase-2 short isoform interacts with membrane-associated cytoskeleton proteins to inhibit apoptosis.
title_sort	caspase-2 short isoform interacts with membrane-associated cytoskeleton proteins to inhibit apoptosis.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/5a3238de228f4574addf29b94dcb9bbf
work_keys_str_mv	AT chunhuahan caspase2shortisoforminteractswithmembraneassociatedcytoskeletonproteinstoinhibitapoptosis AT ranzhao caspase2shortisoforminteractswithmembraneassociatedcytoskeletonproteinstoinhibitapoptosis AT johnkroger caspase2shortisoforminteractswithmembraneassociatedcytoskeletonproteinstoinhibitapoptosis AT meihuaqu caspase2shortisoforminteractswithmembraneassociatedcytoskeletonproteinstoinhibitapoptosis AT altafawani caspase2shortisoforminteractswithmembraneassociatedcytoskeletonproteinstoinhibitapoptosis AT qienwang caspase2shortisoforminteractswithmembraneassociatedcytoskeletonproteinstoinhibitapoptosis
_version_	1718423161543852032

Caspase-2 short isoform interacts with membrane-associated cytoskeleton proteins to inhibit apoptosis.

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