Distinct p63 and p73 Protein Interactions Predict Specific Functions in mRNA Splicing and Polyploidy Control in Epithelia

Epithelial organs are the first barrier against microorganisms and genotoxic stress, in which the p53 family members p63 and p73 have both overlapping and distinct functions. Intriguingly, p73 displays a very specific localization to basal epithelial cells in human tissues, while p63 is expressed in both basal and differentiated cells. Here, we analyse systematically the literature describing p63 and p73 protein–protein interactions to reveal distinct functions underlying the aforementioned distribution. We have found that p73 and p63 cooperate in the genome stability surveillance in proliferating cells; p73 specific interactors contribute to the transcriptional repression, anaphase promoting complex and spindle assembly checkpoint, whereas p63 specific interactors play roles in the regulation of mRNA processing and splicing in both proliferating and differentiated cells. Our analysis reveals the diversification of the RNA and DNA specific functions within the p53 family.

Download Full-text

Protein-protein interactions of the p53 family with the Bcl-2 family in hepatocellular carcinoma

Zeitschrift für Gastroenterologie ◽

10.1055/s-0031-1285581 ◽

2011 ◽

Vol 49 (08) ◽

Author(s):

LC König ◽

M Meinhard ◽

C Sandig ◽

MH Bender ◽

A Lovas ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Protein Interactions ◽

Protein Protein Interactions ◽

P53 Family

Download Full-text

TULP1 and TUB Are Required for Specific Localization of PRCD to Photoreceptor Outer Segments

International Journal of Molecular Sciences ◽

10.3390/ijms21228677 ◽

2020 ◽

Vol 21 (22) ◽

pp. 8677

Author(s):

Lital Remez ◽

Ben Cohen ◽

Mariela J. Nevet ◽

Leah Rizel ◽

Tamar Ben-Yosef

Keyword(s):

Protein Interactions ◽

Mammalian Cells ◽

Outer Segment ◽

Protein Protein Interactions ◽

Photoreceptor Outer Segment ◽

Photoreceptor Outer Segments ◽

Outer Segments ◽

Yeast Two Hybrid System ◽

Specific Localization ◽

Recruitment System

Photoreceptor disc component (PRCD) is a small protein which is exclusively localized to photoreceptor outer segments, and is involved in the formation of photoreceptor outer segment discs. Mutations in PRCD are associated with retinal degeneration in humans, mice, and dogs. The purpose of this work was to identify PRCD-binding proteins in the retina. PRCD protein-protein interactions were identified when implementing the Ras recruitment system (RRS), a cytoplasmic-based yeast two-hybrid system, on a bovine retina cDNA library. An interaction between PRCD and tubby-like protein 1 (TULP1) was identified. Co-immunoprecipitation in transfected mammalian cells confirmed that PRCD interacts with TULP1, as well as with its homolog, TUB. These interactions were mediated by TULP1 and TUB highly conserved C-terminal tubby domain. PRCD localization was altered in the retinas of TULP1- and TUB-deficient mice. These results show that TULP1 and TUB, which are involved in the vesicular trafficking of several photoreceptor proteins from the inner segment to the outer segment, are also required for PRCD exclusive localization to photoreceptor outer segment discs.

Download Full-text

The Role of Posttranslational Modifications in DNA Repair

BioMed Research International ◽

10.1155/2020/7493902 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Miaomiao Bai ◽

Dongdong Ti ◽

Qian Mei ◽

Jiejie Liu ◽

Xin Yan ◽

...

Keyword(s):

Dna Damage ◽

Dna Repair ◽

Protein Interactions ◽

Posttranslational Modifications ◽

Genome Stability ◽

Protein Localization ◽

Complex Structure ◽

Protein Protein Interactions ◽

Regulate Protein

The human body is a complex structure of cells, which are exposed to many types of stress. Cells must utilize various mechanisms to protect their DNA from damage caused by metabolic and external sources to maintain genomic integrity and homeostasis and to prevent the development of cancer. DNA damage inevitably occurs regardless of physiological or abnormal conditions. In response to DNA damage, signaling pathways are activated to repair the damaged DNA or to induce cell apoptosis. During the process, posttranslational modifications (PTMs) can be used to modulate enzymatic activities and regulate protein stability, protein localization, and protein-protein interactions. Thus, PTMs in DNA repair should be studied. In this review, we will focus on the current understanding of the phosphorylation, poly(ADP-ribosyl)ation, ubiquitination, SUMOylation, acetylation, and methylation of six typical PTMs and summarize PTMs of the key proteins in DNA repair, providing important insight into the role of PTMs in the maintenance of genome stability and contributing to reveal new and selective therapeutic approaches to target cancers.

Download Full-text

A silencer is required for maintenance of transcriptional repression throughout Drosophila development

Development ◽

10.1242/dev.124.21.4343 ◽

1997 ◽

Vol 124 (21) ◽

pp. 4343-4350 ◽

Cited By ~ 4

Author(s):

A. Busturia ◽

C.D. Wightman ◽

S. Sakonju

Keyword(s):

Protein Interactions ◽

Transcriptional Repression ◽

Transcriptional Silencing ◽

Active Role ◽

Polycomb Group ◽

Homeotic Genes ◽

Protein Protein Interactions ◽

Drosophila Development ◽

Larval Stages ◽

Associated Proteins

Transcriptional silencing by the Polycomb Group of genes maintains the position-specific repression of homeotic genes throughout Drosophila development. The Polycomb Group of genes characterized to date encode chromatin-associated proteins that have been suggested to form heterochromatin-like structures. By studying the expression of reporter genes, we have identified a 725 bp fragment, called MCP725, in the homeotic gene Abdominal-B, that accurately maintains position-specific silencing during proliferation of imaginal cells. Silencing by MCP725 requires the Polycomb and the Polycomblike genes, indicating that it contains a Polycomb response element To investigate the mechanisms of transcriptional silencing by MCP725, we have studied its temporal requirements by removing MCP725 from the transgene at various times during development. We have discovered that excision of MCP725 during larval stages leads to loss of silencing. Our findings indicate that the silencer is required for the maintenance of the repressed state throughout cell proliferation. They also suggest that propagation of the silenced state does not occur merely by templating of a heterochromatin structure by virtue of protein-protein interactions. Rather, they suggest that silencers play an active role in the maintenance of the position-specific repression throughout development.

Download Full-text

Multiple change in E2F function and regulation occur upon muscle differentiation.

Molecular and Cellular Biology ◽

10.1128/mcb.15.4.2252 ◽

1995 ◽

Vol 15 (4) ◽

pp. 2252-2262 ◽

Cited By ~ 51

Author(s):

E K Shin ◽

A Shin ◽

C Paulding ◽

B Schaffhausen ◽

A S Yee

Keyword(s):

Protein Interactions ◽

Growth Control ◽

Terminal Differentiation ◽

Muscle Differentiation ◽

Protein Protein Interactions ◽

Protein Levels ◽

Differentiated Cells ◽

Prominent Component ◽

Undifferentiated Cells ◽

E2f Transcription Factor

We have examined regulation of the E2F transcription factor during differentiation of muscle cells. E2F regulates many genes involved in growth control and is also the target of regulation by diverse cellular signals, including the RB family of growth suppressors (e.g., the retinoblastoma protein [RB], p107, and p130). The following aspects of E2F function and regulation during muscle differentiation were investigated: (i) protein-protein interactions, (ii) protein levels, (iii) phosphorylation of the E2F protein, and (iv) transcriptional activity. A distinct E2F complex was present in differentiated cells but not in undifferentiated cells. The p130 protein was a prominent component of the E2F complex associated with differentiation. In contrast, in undifferentiated cells, the p107 protein was the prominent component in one of three E2F complexes. In addition, use of a differentiation-defective muscle line provided genetic and biochemical evidence that quiescence and differentiation are separable events. Exclusive formation of the E2F-p130 complex did not occur in this differentiation-defective line; however, E2F complexes diagnostic of quiescence were readily apparent. Thus, sole formation of the E2F-p130 complex is a necessary event in terminal differentiation. Other changes in E2F function and regulation upon differentiation include decreased phosphorylation and increased repression by E2F. These observations suggest that the regulation of E2F function during terminal differentiation may proceed through differential interaction within the RB family and/or phosphorylation.

Download Full-text

057 Understanding the distinct roles of p53 family of transcription factors through identification of protein-protein interactions

Journal of Investigative Dermatology ◽

10.1016/j.jid.2021.02.074 ◽

2021 ◽

Vol 141 (5) ◽

pp. S10

Author(s):

E. Guven Maiorov ◽

K. King ◽

N. Sakakibara ◽

H. Matar ◽

R. Ponnamperuma ◽

...

Keyword(s):

Transcription Factors ◽

Protein Interactions ◽

Protein Protein Interactions ◽

P53 Family

Download Full-text

ZNF224 Protein: Multifaceted Functions Based on Its Molecular Partners

Molecules ◽

10.3390/molecules26206296 ◽

2021 ◽

Vol 26 (20) ◽

pp. 6296

Author(s):

Elena Cesaro ◽

Angelo Lupo ◽

Roberta Rapuano ◽

Arianna Pastore ◽

Michela Grosso ◽

...

Keyword(s):

Dna Binding ◽

Zinc Finger ◽

Protein Interactions ◽

Transcriptional Repression ◽

Zinc Finger Protein ◽

Current Knowledge ◽

Protein Protein Interactions ◽

Multifunctional Protein ◽

Finger Protein ◽

Zinc Finger Domains

The transcription factor ZNF224 is a Kruppel-like zinc finger protein that consists of 707 amino acids and contains 19 tandemly repeated C2H2 zinc finger domains that mediate DNA binding and protein–protein interactions. ZNF224 was originally identified as a transcriptional repressor of genes involved in energy metabolism, and it was demonstrated that ZNF224-mediated transcriptional repression needs the interaction of its KRAB repressor domain with the co-repressor KAP1 and its zinc finger domains 1–3 with the arginine methyltransferase PRMT5. Furthermore, the protein ZNF255 was identified as an alternative isoform of ZNF224 that possesses different domain compositions mediating distinctive functional interactions. Subsequent studies showed that ZNF224 is a multifunctional protein able to exert different transcriptional activities depending on the cell context and the variety of its molecular partners. Indeed, it has been shown that ZNF224 can act as a repressor, an activator and a cofactor for other DNA-binding transcription factors in different human cancers. Here, we provide a brief overview of the current knowledge on the multifaceted interactions of ZNF224 and the resulting different roles of this protein in various cellular contexts.

Download Full-text

In Vivo Assay of Protein-Protein Interactions in Hin-Mediated DNA Inversion

Journal of Bacteriology ◽

10.1128/jb.180.22.5954-5960.1998 ◽

1998 ◽

Vol 180 (22) ◽

pp. 5954-5960 ◽

Cited By ~ 5

Author(s):

Sun Young Lee ◽

Hee Jung Lee ◽

Heejin Lee ◽

Shukho Kim ◽

Eun Hee Cho ◽

...

Keyword(s):

Protein Interactions ◽

Transcriptional Repression ◽

Assay System ◽

Host Cells ◽

Stable Complex ◽

Protein Protein Interactions ◽

Dna Inversion ◽

In Vivo Assay

ABSTRACT In order to form the catalytic nucleoprotein complex called the invertasome in the Hin-mediated DNA inversion reaction, interactions of the DNA-binding proteins Hin and Fis are required. Assays for these protein-protein interactions have been exploited with protein cross-linkers in vitro. In this study, an in vivo assay system that probes protein-protein interactions was developed. The formation of a DNA loop generated by protein interactions resulted in transcriptional repression of an artificially designed operon, which in turn increased the chance of survival of Escherichia colihost cells in a streptomycin-containing medium. Using this system, we were able to assay the Hin-Hin interaction that results in the pairing of the two recombination sites and protein interactions that result in the formation of the invertasome. This assay system also led us to find that an individual Hin dimer bound on a recombination site can form a stable complex with Fis bound on the recombinational enhancer; this finding has never been observed in in vitro studies. Possible pathways toward the formation of the invertasome are discussed based on the assay results for a previously reported Hin mutant.

Download Full-text

Shugoshin promotes efficient activation of spindle assembly checkpoint and timely spindle disassembly

10.1101/2020.09.04.282871 ◽

2020 ◽

Author(s):

Aakanksha Sane ◽

Shreyas Sridhar ◽

Kaustuv Sanyal ◽

Santanu K Ghosh

Keyword(s):

Protein Interactions ◽

Spindle Assembly Checkpoint ◽

Spindle Assembly ◽

Protein Protein Interactions ◽

Cellular Functions ◽

Spindle Disassembly ◽

Spatio Temporal ◽

Species Specific ◽

Chromosome Passenger Complex

AbstractShugoshin proteins are evolutionary conserved across eukaryotes with some species-specific cellular functions ensuring the fidelity of chromosome segregation. Shugoshin being present at various subcellular locales, acts as an adaptor to mediate various protein-protein interactions in a spatio-temporal manner. Here, we characterize shugoshin (Sgo1) in the human fungal pathogen, Candida albicans. Interestingly, we discover a novel in vivo localization of Sgo1 along the length of the mitotic spindle. Further, Sgo1 performs a hitherto unknown function of facilitating timely disassembly of spindle in this organism. We observe that Sgo1 retains its centromeric localization and performs its conserved functions that include regulating the centromeric condensin localization, chromosome passenger complex (CPC) maintenance and sister chromatid biorientation. We identify novel roles of Sgo1 as a spindle assembly checkpoint (SAC) component with functions in maintaining the SAC proteins, Mad2 and Bub1, at the kinetochores, in response to faulty kinetochore-microtubule attachments. These findings provide an excellent evidence of the functional rewiring of shugoshin in maintaining genomic stability.

Download Full-text

Activation of the Early B-Cell-Specific mb-1 (Ig-α) Gene by Pax-5 Is Dependent on an Unmethylated Ets Binding Site

Molecular and Cellular Biology ◽

10.1128/mcb.23.6.1946-1960.2003 ◽

2003 ◽

Vol 23 (6) ◽

pp. 1946-1960 ◽

Cited By ~ 71

Author(s):

Holly Maier ◽

Jeff Colbert ◽

Daniel Fitzsimmons ◽

Dawn R. Clark ◽

James Hagman

Keyword(s):

B Cell ◽

Protein Interactions ◽

Transcriptional Repression ◽

Antisense Strand ◽

Protein Protein Interactions ◽

Mobility Shift ◽

Cpg Dinucleotides ◽

Ets Proteins ◽

B Lineage ◽

Electrophoretic Mobility Shift Assays

ABSTRACT Methylation of cytosine in CpG dinucleotides promotes transcriptional repression in mammals by blocking transcription factor binding and recruiting methyl-binding proteins that initiate chromatin remodeling. Here, we use a novel cell-based system to show that retrovirally expressed Pax-5 protein activates endogenous early B-cell-specific mb-1 genes in plasmacytoma cells, but only when the promoter is hypomethylated. CpG methylation does not directly affect binding of the promoter by Pax-5. Instead, methylation of an adjacent CpG interferes with assembly of ternary complexes comprising Pax-5 and Ets proteins. In electrophoretic mobility shift assays, recruitment of Ets-1 is blocked by methylation of the Ets site (5′CCGGAG) on the antisense strand. In transfection assays, selective methylation of a single CpG within the Pax-5-dependent Ets site greatly reduces mb-1 promoter activity. Prior demethylation of the endogenous mb-1 promoter is required for its activation by Pax-5 in transduced cells. Although B-lineage cells have only unmethylated mb-1 genes and do not modulate methylation of the mb-1 promoter during development, other tissues feature high percentages of methylated alleles. Together, these studies demonstrate a novel DNA methylation-dependent mechanism for regulating transcriptional activity through the inhibition of DNA-dependent protein-protein interactions.

Download Full-text