| Title : A flow cytometry-based screen of nuclear envelope transmembrane proteins identifies NET4\/Tmem53 as involved in stress-dependent cell cycle withdrawal - Korfali_2011_PLoS.One_6_e18762 |
| Author(s) : Korfali N , Srsen V , Waterfall M , Batrakou DG , Pekovic V , Hutchison CJ , Schirmer EC |
| Ref : PLoS ONE , 6 :e18762 , 2011 |
| Abstract : Disruption of cell cycle regulation is one mechanism proposed for how nuclear envelope protein mutation can cause disease. Thus far only a few nuclear envelope proteins have been tested/found to affect cell cycle progression: to identify others, 39 novel nuclear envelope transmembrane proteins were screened for their ability to alter flow cytometry cell cycle/DNA content profiles when exogenously expressed. Eight had notable effects with seven increasing and one decreasing the 4N:2N ratio. We subsequently focused on NET4/Tmem53 that lost its effects in p53(-/-) cells and retinoblastoma protein-deficient cells. NET4/TMEM53 knockdown by siRNA altered flow cytometry cell cycle/DNA content profiles in a similar way as overexpression. NET4/TMEM53 knockdown did not affect total retinoblastoma protein levels, unlike nuclear envelope-associated proteins Lamin A and LAP2alpha. However, a decrease in phosphorylated retinoblastoma protein was observed along with a doubling of p53 levels and a 7-fold increase in p21. Consequently cells withdrew from the cell cycle, which was confirmed in MRC5 cells by a drop in the percentage of cells expressing Ki-67 antigen and an increase in the number of cells stained for ss-galactosidase. The ss-galactosidase upregulation suggests that cells become prematurely senescent. Finally, the changes in retinoblastoma protein, p53, and p21 resulting from loss of NET4/Tmem53 were dependent upon active p38 MAP kinase. The finding that roughly a fifth of nuclear envelope transmembrane proteins screened yielded alterations in flow cytometry cell cycle/DNA content profiles suggests a much greater influence of the nuclear envelope on the cell cycle than is widely held. |
| ESTHER : Korfali_2011_PLoS.One_6_e18762 |
| PubMedSearch : Korfali_2011_PLoS.One_6_e18762 |
| PubMedID: 21533191 |
| Gene_locus related to this paper: human-TMEM53 |
| Gene_locus related to this paper: human-TMEM53 |
Korfali N, Srsen V, Waterfall M, Batrakou DG, Pekovic V, Hutchison CJ, Schirmer EC (2011)
A flow cytometry-based screen of nuclear envelope transmembrane proteins identifies NET4\/Tmem53 as involved in stress-dependent cell cycle withdrawal
PLoS ONE
6 :e18762
Korfali N, Srsen V, Waterfall M, Batrakou DG, Pekovic V, Hutchison CJ, Schirmer EC (2011)
PLoS ONE
6 :e18762