Hmga1 null mouse embryonic fibroblasts display downregulation of spindle assembly checkpoint gene expression associated to nuclear and karyotypic abnormalities

Giovanna Maria Pierantoni; Andrea Conte; Cinzia Rinaldo; Mara Tornincasa; Raffaele Gerlini; Davide Valente; Antonella Izzo; Alfredo Fusco

doi:10.1080/15384101.2016.1146835

Hmga1 null mouse embryonic fibroblasts display downregulation of spindle assembly checkpoint gene expression associated to nuclear and karyotypic abnormalities

Cell Cycle. 2016;15(6):812-8. doi: 10.1080/15384101.2016.1146835.

Authors

Giovanna Maria Pierantoni¹, Andrea Conte¹, Cinzia Rinaldo², Mara Tornincasa¹, Raffaele Gerlini¹, Davide Valente², Antonella Izzo¹, Alfredo Fusco¹

Affiliations

¹ a Istituto di Endocrinologia ed Oncologia Sperimentale del CNR and Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli "Federico II" , Naples , Italy.
² b Istituto di Biologia e Patologie Molecolari del CNR c/o Università "Sapienza" di Roma , Rome , Italy.

Abstract

The High Mobility Group A1 proteins (HMGA1) are nonhistone chromatinic proteins with a critical role in development and cancer. We have recently reported that HMGA1 proteins are able to increase the expression of spindle assembly checkpoint (SAC) genes, thus impairing SAC function and causing chromosomal instability in cancer cells. Moreover, we found a significant correlation between HMGA1 and SAC genes expression in human colon carcinomas. Here, we report that mouse embryonic fibroblasts null for the Hmga1 gene show downregulation of Bub1, Bub1b, Mad2l1 and Ttk SAC genes, and present several features of chromosomal instability, such as nuclear abnormalities, binucleation, micronuclei and karyotypic alterations. Interestingky, also MEFs carrying only one impaired Hmga1 allele present karyotypic alterations. These results indicate that HMGA1 proteins regulate SAC genes expression and, thereby, genomic stability also in embryonic cells.

Keywords: Chromosome instability; HMGA1; SAC.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing / genetics
Adaptor Proteins, Signal Transducing / metabolism
Animals
Cell Cycle Proteins / genetics
Cell Cycle Proteins / metabolism
Cell Nucleus / genetics
Cell Nucleus / pathology
Chromosomal Instability*
Embryo, Mammalian
Fibroblasts / metabolism*
Fibroblasts / pathology
G2 Phase Cell Cycle Checkpoints*
Gene Expression Regulation
Genetic Complementation Test
HMGA1a Protein / deficiency
HMGA1a Protein / genetics*
Karyotype
M Phase Cell Cycle Checkpoints / genetics*
Mice
Mice, Knockout
Micronuclei, Chromosome-Defective
Nuclear Proteins / genetics
Nuclear Proteins / metabolism
Protein Serine-Threonine Kinases / genetics
Protein Serine-Threonine Kinases / metabolism
Signal Transduction

Substances

Adaptor Proteins, Signal Transducing
Bub1b protein, mouse
Cell Cycle Proteins
Mad2l1bp protein, mouse
Nuclear Proteins
HMGA1a Protein
Ttk protein, mouse
Bub1 protein, mouse
Protein Serine-Threonine Kinases