scholarly journals Critical Role of the Ubiquitin Ligase Activity of UHRF1, a Nuclear RING Finger Protein, in Tumor Cell Growth

2005 ◽  
Vol 16 (12) ◽  
pp. 5621-5629 ◽  
Author(s):  
Yonchu Jenkins ◽  
Vadim Markovtsov ◽  
Wayne Lang ◽  
Poonam Sharma ◽  
Denise Pearsall ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Tumor Cell ◽  
A549 Cells ◽  
Ring Finger ◽  
Cell Cycle Checkpoints ◽  
Ring Finger Protein ◽  
E3 Ligases ◽  
Finger Protein ◽  
Nuclear Ring

Early cellular events associated with tumorigenesis often include loss of cell cycle checkpoints or alteration in growth signaling pathways. Identification of novel genes involved in cellular proliferation may lead to new classes of cancer therapeutics. By screening a tetracycline-inducible cDNA library in A549 cells for genes that interfere with proliferation, we have identified a fragment of UHRF1 (ubiquitin-like protein containing PHD and RING domains 1), a nuclear RING finger protein, that acts as a dominant negative effector of cell growth. Reduction of UHRF1 levels using an UHRF1-specific shRNA decreased growth rates in several tumor cell lines. In addition, treatment of A549 cells with agents that activated different cell cycle checkpoints resulted in down-regulation of UHRF1. The primary sequence of UHRF1 contains a PHD and a RING motif, both of which are structural hallmarks of ubiquitin E3 ligases. We have confirmed using an in vitro autoubiquitination assay that UHRF1 displays RING-dependent E3 ligase activity. Overexpression of a GFP-fused UHRF1 RING mutant that lacks ligase activity sensitizes cells to treatment with various chemotherapeutics. Taken together, our results suggest a general requirement for UHRF1 in tumor cell proliferation and implicate the RING domain of UHRF1 as a functional determinant of growth regulation.

scholarly journals Metastasis-associated protein 1 drives tumor cell migration and invasion through transcriptional repression of RING finger protein 144A.: FIGURE 3.

2012 ◽  
Vol 287 (15) ◽  
pp. 12158-12158
Author(s):  
Hezlin Marzook ◽  
Da-Qiang Li ◽  
Vasudha S. Nair ◽  
Prakriti Mudvari ◽  
Sirigiri Divijendra Natha Reddy ◽  
...  
Keyword(s):  
Cell Migration ◽  
Tumor Cell ◽  
Transcriptional Repression ◽  
Ring Finger ◽  
Migration And Invasion ◽  
Ring Finger Protein ◽  
Cell Migration And Invasion ◽  
Tumor Cell Migration ◽  
Finger Protein

scholarly journals MBLR, a new RING finger protein resembling mammalian Polycomb gene products, is regulated by cell cycle-dependent phosphorylation

2002 ◽  
Vol 7 (8) ◽  
pp. 835-850 ◽  
Author(s):  
Takeshi Akasaka ◽  
Naomi Takahashi ◽  
Maki Suzuki ◽  
Haruhiko Koseki ◽  
Rolf Bodmer ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ring Finger ◽  
Gene Products ◽  
Ring Finger Protein ◽  
Finger Protein ◽  
Cycle Dependent

scholarly journals Metastasis-associated Protein 1 Drives Tumor Cell Migration and Invasion through Transcriptional Repression of RING Finger Protein 144A

2011 ◽  
Vol 287 (8) ◽  
pp. 5615-5626 ◽  
Author(s):  
Hezlin Marzook ◽  
Da-Qiang Li ◽  
Vasudha S. Nair ◽  
Prakriti Mudvari ◽  
Sirigiri Divijendra Natha Reddy ◽  
...  
Keyword(s):  
Cell Migration ◽  
Tumor Cell ◽  
Transcriptional Repression ◽  
Ring Finger ◽  
Migration And Invasion ◽  
Ring Finger Protein ◽  
Cell Migration And Invasion ◽  
Tumor Cell Migration ◽  
Finger Protein

scholarly journals Metastasis-associated protein 1 drives tumor cell migration and invasion through transcriptional repression of RING finger protein 144A.

2015 ◽  
Vol 290 (11) ◽  
pp. 6751-6751 ◽  
Author(s):  
Hezlin Marzook ◽  
Da-Qiang Li ◽  
Vasudha S. Nair ◽  
Prakriti Mudvari ◽  
Sirigiri Divijendra Natha Reddy ◽  
...  
Keyword(s):  
Cell Migration ◽  
Tumor Cell ◽  
Transcriptional Repression ◽  
Ring Finger ◽  
Migration And Invasion ◽  
Ring Finger Protein ◽  
Cell Migration And Invasion ◽  
Tumor Cell Migration ◽  
Finger Protein

Targeting the Cell Cycle: A New Approach to Cancer Therapy

2005 ◽  
Vol 23 (36) ◽  
pp. 9408-9421 ◽  
Author(s):  
Gary K. Schwartz ◽  
Manish A. Shah
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Tumor Cell ◽  
Critical Time ◽  
Cell Cycle Checkpoints ◽  
New Approach ◽  
Cyclin Dependent Kinases ◽  
Cycle Arrest ◽  
Induce Growth Arrest ◽  
Apoptotic Cascade

The cell cycle represents a series of tightly integrated events that allow the cell to grow and proliferate. Critical parts of the cell cycle machinery are the cyclin-dependent kinases (CDKs), which, when activated, provide a means for the cell to move from one phase of the cell cycle to the next. The CDKs are regulated positively by cyclins and regulated negatively by naturally occurring CDK inhibitors (CDKIs). Cancer represents a dysregulation of the cell cycle such that cells that overexpress cyclins or do not express the CDKIs continue to undergo unregulated cell growth. The cell cycle also serves to protect the cell from DNA damage. Thus, cell cycle arrest, in fact, represents a survival mechanism that provides the tumor cell the opportunity to repair its own damaged DNA. Thus, abrogation of cell cycle checkpoints, before DNA repair is complete, can activate the apoptotic cascade, leading to cell death. Now in clinical trials are a series of targeted agents that directly inhibit the CDKs, inhibit unrestricted cell growth, and induce growth arrest. Recent attention has also focused on these drugs as inhibitors of transcription. In addition, there are now agents that abrogate the cell cycle checkpoints at critical time points that make the tumor cell susceptible to apoptosis. An understanding of the cell cycle is critical to understanding how best to clinically develop these agents, both as single agents and in combination with chemotherapy.

scholarly journals miR-762 promotes porcine immature Sertoli cell growth via the ring finger protein 4 (RNF4) gene

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Changping Ma ◽  
Huibin Song ◽  
Lei Yu ◽  
Kaifeng Guan ◽  
Pandi Hu ◽  
...  
Keyword(s):  
Cell Growth ◽  
Sertoli Cell ◽  
Ring Finger ◽  
Ring Finger Protein ◽  
Finger Protein

scholarly journals Small Nuclear RING Finger Protein Expression during Gonad Development: Regulation by Gonadotropins and Estrogen in the Postnatal Ovary

Endocrinology ◽  
2004 ◽  
Vol 145 (5) ◽  
pp. 2433-2444 ◽  
Author(s):  
Sirpa J. Hirvonen-Santti ◽  
Venkataraman Sriraman ◽  
Mikko Anttonen ◽  
Saija Savolainen ◽  
Jorma J. Palvimo ◽  
...  
Keyword(s):  
Protein Expression ◽  
Gonad Development ◽  
Ring Finger ◽  
Ring Finger Protein ◽  
Finger Protein ◽  
Nuclear Ring ◽  
Development Regulation

scholarly journals Screen for multi-SUMO–binding proteins reveals a multi-SIM–binding mechanism for recruitment of the transcriptional regulator ZMYM2 to chromatin

2015 ◽  
Vol 112 (35) ◽  
pp. E4854-E4863 ◽  
Author(s):  
Elisa Aguilar-Martinez ◽  
Xi Chen ◽  
Aaron Webber ◽  
A. Paul Mould ◽  
Anne Seifert ◽  
...  
Keyword(s):  
Transcriptional Control ◽  
Ring Finger ◽  
Binding Activity ◽  
Ring Finger Protein ◽  
E3 Ligases ◽  
Binding Partner ◽  
Finger Protein ◽  
Sumo Binding Proteins ◽  
Nuclear Processes ◽  
Regulatory Event

Protein SUMOylation has emerged as an important regulatory event, particularly in nuclear processes such as transcriptional control and DNA repair. In this context, small ubiquitin-like modifier (SUMO) often provides a binding platform for the recruitment of proteins via their SUMO-interacting motifs (SIMs). Recent discoveries point to an important role for multivalent SUMO binding through multiple SIMs in the binding partner as exemplified by poly-SUMOylation acting as a binding platform for ubiquitin E3 ligases such as ring finger protein 4. Here, we have investigated whether other types of protein are recruited through multivalent SUMO interactions. We have identified dozens of proteins that bind to multi-SUMO platforms, thereby uncovering a complex potential regulatory network. Multi-SUMO binding is mediated through multi-SIM modules, and the functional importance of these interactions is demonstrated for the transcriptional corepressor ZMYM2/ZNF198 where its multi-SUMO–binding activity is required for its recruitment to chromatin.

The RING finger protein SNURF modulates nuclear trafficking of the androgen receptor

2000 ◽  
Vol 113 (17) ◽  
pp. 2991-3001 ◽  
Author(s):  
H. Poukka ◽  
U. Karvonen ◽  
N. Yoshikawa ◽  
H. Tanaka ◽  
J.J. Palvimo ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Fluorescent Protein ◽  
Ring Finger ◽  
Ring Finger Protein ◽  
Nuclear Trafficking ◽  
Finger Protein ◽  
Androgen Exposure ◽  
Nuclear Ring ◽  
Localization Signal ◽  
Green Fluorescent

The androgen receptor (AR) is a transcription factor that mediates androgen action. We have used the green fluorescent protein (GFP) technique to investigate dynamics of nuclear trafficking of human AR in living cells. In the absence of ligand, the GFP-AR fusion protein is distributed between cytoplasm and nuclei. Androgen exposure leads to a rapid and complete import of GFP-AR to nuclei of CV-1 cells (>=90% nuclear in 30 minutes), whereas a pure antiandrogen, Casodex, elicits a slower (<40% nuclear in 30 minutes) and incomplete transfer. Unliganded ARs with mutations in the basic amino acids of the bipartite nuclear localization signal (NLS) within the second zinc finger and the hinge region are predominantly cytoplasmic and their androgen-dependent nuclear import is severely compromised ((3/4)20% nuclear in 30 minutes). Interestingly, substitutions of the Leu residues flanking the bipartite NLS lead to inefficient nuclear transfer in response to androgen ((3/4)20% nuclear in 30 minutes). The ligand-binding domain of AR, which represses bipartite NLS activity, contains an agonist-specific NLS. The small nuclear RING finger protein SNURF, which interacts with AR through a region overlapping with the bipartite NLS, facilitates AR import to nuclei and retards its export on hormone withdrawal. More AR is associated with the nuclear matrix in the presence than absence of coexpressed SNURF. We suggest that the SNURF-mediated tethering of AR in nuclei represents a novel mechanism for activating steroid receptor functions.

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