Universität zu Köln

Leone, Marina ORCID: 0000-0001-6839-6265, Cazorla-Vazquez, Salvador, Ferrazzi, Fulvia ORCID: 0000-0003-4011-4638, Wiederstein, Janica L., Gruendl, Marco, Weinstock, Grit, Vergarajauregui, Silvia ORCID: 0000-0002-9247-6123, Eckstein, Markus, Krueger, Marcus, Gaubatz, Stefan ORCID: 0000-0001-8751-4191 and Engel, Felix B. ORCID: 0000-0003-2605-3429 (2021). IQGAP3, a YAP Target, Is Required for Proper Cell-Cycle Progression and Genome Stability. Mol. Cancer Res., 19 (10). S. 1712 - 1727. PHILADELPHIA: AMER ASSOC CANCER RESEARCH. ISSN 1557-3125

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Abstract

Controlling cell proliferation is critical for organism development, tissue homeostasis, disease, and regeneration. IQGAP3 has been shown to be required for proper cell proliferation and migration, and is associated to a number of cancers. Moreover, its expression is inversely correlated with the overall survival rate in the majority of cancers. Here, we show that IQGAP3 expression is elevated in cervical cancer and that in these cancers IQGAP3 high expression is correlated with an increased lethality. Furthermore, we demonstrate that IQGAP3 is a target of YAP, a regulator of cell cycle gene expression. IQGAP3 knockdown resulted in an increased percentage of HeLa cells in S phase, delayed progression through mitosis, and caused multipolar spindle formation and consequentially aneuploidy. Protein-protein interaction studies revealed that IQGAP3 interacts with MMS19, which is known in Drosophila to permit, by competitive binding to Xpd, Cdk7 to be fully active as a Cdk-activating kinase (CAK). Notably, IQGAP3 knockdown caused decreased MMS19 protein levels and XPD knockdown partially rescued the reduced proliferation rate upon IQGAP3 knockdown. This suggests that IQGAP3 modulates the cell cycle via the MMS19/XPD/CAK axis. Thus, in addition to governing proliferation and migration, IQGAP3 is a critical regulator of mitotic progression and genome stability.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Leone, Marina UNSPECIFIED orcid.org/0000-0001-6839-6265 UNSPECIFIED Cazorla-Vazquez, Salvador UNSPECIFIED UNSPECIFIED UNSPECIFIED Ferrazzi, Fulvia UNSPECIFIED orcid.org/0000-0003-4011-4638 UNSPECIFIED Wiederstein, Janica L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gruendl, Marco UNSPECIFIED UNSPECIFIED UNSPECIFIED Weinstock, Grit UNSPECIFIED UNSPECIFIED UNSPECIFIED Vergarajauregui, Silvia UNSPECIFIED orcid.org/0000-0002-9247-6123 UNSPECIFIED Eckstein, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Krueger, Marcus UNSPECIFIED UNSPECIFIED UNSPECIFIED Gaubatz, Stefan UNSPECIFIED orcid.org/0000-0001-8751-4191 UNSPECIFIED Engel, Felix B. UNSPECIFIED orcid.org/0000-0003-2605-3429 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-592138
DOI:	10.1158/1541-7786.MCR-20-0639
Journal or Publication Title:	Mol. Cancer Res.
Volume:	19
Number:	10
Page Range:	S. 1712 - 1727
Date:	2021
Publisher:	AMER ASSOC CANCER RESEARCH
Place of Publication:	PHILADELPHIA
ISSN:	1557-3125
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HIPPO PATHWAY; PROLIFERATION; PHOSPHORYLATION; TRANSCRIPTION; CONTRIBUTES; INVOLVEMENT; INHIBITION; ACTIVATION; PROTEINS; COMPLEX Multiple languages Oncology; Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59213