scholarly journals The Retinoblastoma Tumor Suppressor Is Required for the NUP98-HOXA9-Induced Aberrant Nuclear Envelope Phenotype

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2851
Author(s):  
Marcela Vaz ◽  
Birthe Fahrenkrog
Keyword(s):  
Tumor Suppressor ◽  
Nuclear Envelope ◽  
Fusion Proteins ◽  
Nuclear Architecture ◽  
Nuclear Lamina ◽  
Dependent Manner ◽  
Morphological Alterations ◽  
Human Papillomavirus 16 ◽  
Retinoblastoma Tumor Suppressor ◽  
Retinoblastoma Tumor

Chromosomal translocations involving the nucleoporin NUP98 gene are recurrently identified in leukemia; yet, the cellular defects accompanying NUP98 fusion proteins are poorly characterized. NUP98 fusions cause changes in nuclear and nuclear envelope (NE) organization, in particular, in the nuclear lamina and the lamina associated polypeptide 2α (LAP2α), a regulator of the tumor suppressor retinoblastoma protein (RB). We demonstrate that, for NUP98-HOXA9 (NHA9), the best-studied NUP98 fusion protein, its effect(s) on nuclear architecture largely depend(s) on RB. Morphological alterations caused by the expression of NHA9 are largely diminished in the absence of RB, both in human cells expressing the human papillomavirus 16 E7 protein and in mouse embryonic fibroblasts lacking RB. We further show that NHA9 expression associates with distinct histone modification. Moreover, the pattern of trimethylation of histone H3 lysine-27 is affected by NHA9, again in an RB-dependent manner. Our results pinpoint to an unexpected interplay between NUP98 fusion proteins and RB, which may contribute to leukemogenesis.

scholarly journals Conserved Region 3 of Human Papillomavirus 16 E7 Contributes to Deregulation of the Retinoblastoma Tumor Suppressor

2012 ◽  
Vol 86 (24) ◽  
pp. 13313-13323 ◽  
Author(s):  
B. Todorovic ◽  
K. Hung ◽  
P. Massimi ◽  
N. Avvakumov ◽  
F. A. Dick ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Tumor Suppressor ◽  
Human Papillomavirus 16 ◽  
Retinoblastoma Tumor Suppressor ◽  
Conserved Region ◽  
Retinoblastoma Tumor

scholarly journals Retinoblastoma tumor suppressor protein–dependent methylation of histone H3 lysine 27 is associated with irreversible cell cycle exit

2007 ◽  
Vol 179 (7) ◽  
pp. 1399-1412 ◽  
Author(s):  
Alexandre Blais ◽  
Chris J.C. van Oevelen ◽  
Raphaël Margueron ◽  
Diego Acosta-Alvear ◽  
Brian David Dynlacht
Keyword(s):  
Cell Cycle ◽  
Tumor Suppressor ◽  
Histone H3 ◽  
Tumor Suppressor Protein ◽  
Dependent Manner ◽  
Cell Cycle Exit ◽  
Retinoblastoma Tumor Suppressor Protein ◽  
Retinoblastoma Tumor Suppressor ◽  
Permanent Cell ◽  
Retinoblastoma Tumor

The retinoblastoma tumor suppressor protein (pRb) is involved in mitotic exit, promoting the arrest of myoblasts, and myogenic differentiation. However, it is unclear how permanent cell cycle exit is maintained in differentiated muscle. Using RNA interference, expression profiling, and chromatin immunoprecipitations, we show that pRb is essential for cell cycle exit and the differentiation of myoblasts and is also uniquely required to maintain this arrest in myotubes. Remarkably, we also uncover a function for the pRb-related proteins p107 and p130 as enforcers of a G2/M phase checkpoint that prevents progression into mitosis in cells that have lost pRb. We further demonstrate that pRb effects permanent cell cycle exit in part by maintaining trimethylation of histone H3 lysine 27 (H3K27) on cell cycle genes. H3K27 trimethylation silences other genes, including Cyclin D1, in a pRb-independent but polycomb-dependent manner. Thus, our data distinguish two distinct chromatin-based regulatory mechanisms that lead to terminal differentiation.

scholarly journals Degradation of the Retinoblastoma Tumor Suppressor by the Human Papillomavirus Type 16 E7 Oncoprotein Is Important for Functional Inactivation and Is Separable from Proteasomal Degradation of E7

2001 ◽  
Vol 75 (16) ◽  
pp. 7583-7591 ◽  
Author(s):  
Sonia L. Gonzalez ◽  
Matt Stremlau ◽  
Xi He ◽  
John R. Basile ◽  
Karl Münger
Keyword(s):  
Human Papillomavirus ◽  
Tumor Suppressor ◽  
Selection Process ◽  
State Level ◽  
Proteasomal Degradation ◽  
Biological Indicator ◽  
26S Proteasome ◽  
Amino Terminal ◽  
Retinoblastoma Tumor Suppressor ◽  
Retinoblastoma Tumor

ABSTRACT The steady-state level and metabolic half-life of retinoblastoma tumor suppressor protein pRB are decreased in cells that express high-risk human papillomavirus (HPV) E7 proteins. Here we show that pRB degradation is a direct activity of E7 and does not reflect a property of cell lines acquired during the selection process for E7 expression. An amino-terminal domain of E7 that does not directly contribute to pRB binding but is required for transformation is also necessary for E7-mediated pRB degradation. Treatment with inhibitors of the 26S proteasome not only blocks E7-mediated pRB degradation but also causes the stabilization of E7. Mutagenic analyses, however, reveal that the processes of proteasomal degradation of E7 and pRB are not linked processes. HPV type 16 E7 also targets the pRB-related proteins p107 and p130 for destabilization by a proteasome-dependent mechanism. Using the SAOS2 flat-cell assay as a biological indicator for pRB function, we demonstrate that pRB degradation, not solely binding, is important for the E7-induced inactivation of pRB.

Sign in / Sign up

Export Citation Format

Share Document