An Alternative Splice Variant of HIPK2 with Intron Retention Contributes to Cytokinesis
HIPK2 is a DYRK-like kinase involved in cellular stress response pathways, development, and cell division. Two alternative splice variants of HIPK2, HIPK2-FL and HIPK2-Δe8, have been previously identified as having different protein stability but similar functional activity in the stress re...
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doaj-b5fcd4f05f56494e9196691901c69c942020-11-25T00:37:16ZengMDPI AGCells2073-44092020-02-019248410.3390/cells9020484cells9020484An Alternative Splice Variant of HIPK2 with Intron Retention Contributes to CytokinesisVeronica Gatti0Manuela Ferrara1Ilaria Virdia2Silvia Matteoni3Laura Monteonofrio4Simona di Martino5Maria Grazia Diodoro6Giuliana Di Rocco7Cinzia Rinaldo8Silvia Soddu9Unit of Cellular Networks and Molecular Therapeutic Targets; IRCCS-Regina Elena National Cancer Institute, 00144 Rome, ItalyInstitute of Molecular Biology and Pathology (IBPM), National Research Council (CNR), c/o Sapienza University, 00185 Rome, ItalyUnit of Cellular Networks and Molecular Therapeutic Targets; IRCCS-Regina Elena National Cancer Institute, 00144 Rome, ItalyUnit of Cellular Networks and Molecular Therapeutic Targets; IRCCS-Regina Elena National Cancer Institute, 00144 Rome, ItalyUnit of Cellular Networks and Molecular Therapeutic Targets; IRCCS-Regina Elena National Cancer Institute, 00144 Rome, ItalyPathology Unit, IRCCS-Regina Elena National Cancer Institute, 00144 Rome, ItalyPathology Unit, IRCCS-Regina Elena National Cancer Institute, 00144 Rome, ItalyUnit of Cellular Networks and Molecular Therapeutic Targets; IRCCS-Regina Elena National Cancer Institute, 00144 Rome, ItalyUnit of Cellular Networks and Molecular Therapeutic Targets; IRCCS-Regina Elena National Cancer Institute, 00144 Rome, ItalyUnit of Cellular Networks and Molecular Therapeutic Targets; IRCCS-Regina Elena National Cancer Institute, 00144 Rome, ItalyHIPK2 is a DYRK-like kinase involved in cellular stress response pathways, development, and cell division. Two alternative splice variants of HIPK2, HIPK2-FL and HIPK2-Δe8, have been previously identified as having different protein stability but similar functional activity in the stress response. Here, we describe one additional HIPK2 splice variant with a distinct subcellular distribution and functional activity in cytokinesis. This novel splice variant lacks the last two exons and retains intron13 with a stop codon after 89 bp of the intron, generating a short isoform, HIPK2-S, that is detectable by 2D Western blots. RT-PCR analyses of tissue arrays and tumor samples show that HIPK2-FL and HIPK2-S are expressed in normal human tissues in a tissue-dependent manner and differentially expressed in human colorectal and pancreatic cancers. Gain- and loss-of-function experiments showed that in contrast to HIPK2-FL, HIPK2-S has a diffuse, non-speckled distribution and is not involved in the DNA damage response. Rather, we found that HIPK2-S, but not HIPK2-FL, localizes at the intercellular bridge, where it phosphorylates histone H2B and spastin, both required for faithful cell division. Altogether, these data show that distinct human HIPK2 splice variants are involved in distinct HIPK2-regulated functions like stress response and cytokinesis.https://www.mdpi.com/2073-4409/9/2/484hipk2 isoformsalternative splicingabscissionfaithful cytokinesiscolorectal cancerpancreatic cancer |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Veronica Gatti Manuela Ferrara Ilaria Virdia Silvia Matteoni Laura Monteonofrio Simona di Martino Maria Grazia Diodoro Giuliana Di Rocco Cinzia Rinaldo Silvia Soddu |
spellingShingle |
Veronica Gatti Manuela Ferrara Ilaria Virdia Silvia Matteoni Laura Monteonofrio Simona di Martino Maria Grazia Diodoro Giuliana Di Rocco Cinzia Rinaldo Silvia Soddu An Alternative Splice Variant of HIPK2 with Intron Retention Contributes to Cytokinesis Cells hipk2 isoforms alternative splicing abscission faithful cytokinesis colorectal cancer pancreatic cancer |
author_facet |
Veronica Gatti Manuela Ferrara Ilaria Virdia Silvia Matteoni Laura Monteonofrio Simona di Martino Maria Grazia Diodoro Giuliana Di Rocco Cinzia Rinaldo Silvia Soddu |
author_sort |
Veronica Gatti |
title |
An Alternative Splice Variant of HIPK2 with Intron Retention Contributes to Cytokinesis |
title_short |
An Alternative Splice Variant of HIPK2 with Intron Retention Contributes to Cytokinesis |
title_full |
An Alternative Splice Variant of HIPK2 with Intron Retention Contributes to Cytokinesis |
title_fullStr |
An Alternative Splice Variant of HIPK2 with Intron Retention Contributes to Cytokinesis |
title_full_unstemmed |
An Alternative Splice Variant of HIPK2 with Intron Retention Contributes to Cytokinesis |
title_sort |
alternative splice variant of hipk2 with intron retention contributes to cytokinesis |
publisher |
MDPI AG |
series |
Cells |
issn |
2073-4409 |
publishDate |
2020-02-01 |
description |
HIPK2 is a DYRK-like kinase involved in cellular stress response pathways, development, and cell division. Two alternative splice variants of HIPK2, HIPK2-FL and HIPK2-Δe8, have been previously identified as having different protein stability but similar functional activity in the stress response. Here, we describe one additional HIPK2 splice variant with a distinct subcellular distribution and functional activity in cytokinesis. This novel splice variant lacks the last two exons and retains intron13 with a stop codon after 89 bp of the intron, generating a short isoform, HIPK2-S, that is detectable by 2D Western blots. RT-PCR analyses of tissue arrays and tumor samples show that HIPK2-FL and HIPK2-S are expressed in normal human tissues in a tissue-dependent manner and differentially expressed in human colorectal and pancreatic cancers. Gain- and loss-of-function experiments showed that in contrast to HIPK2-FL, HIPK2-S has a diffuse, non-speckled distribution and is not involved in the DNA damage response. Rather, we found that HIPK2-S, but not HIPK2-FL, localizes at the intercellular bridge, where it phosphorylates histone H2B and spastin, both required for faithful cell division. Altogether, these data show that distinct human HIPK2 splice variants are involved in distinct HIPK2-regulated functions like stress response and cytokinesis. |
topic |
hipk2 isoforms alternative splicing abscission faithful cytokinesis colorectal cancer pancreatic cancer |
url |
https://www.mdpi.com/2073-4409/9/2/484 |
work_keys_str_mv |
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