Monomeric but not trimeric clathrin heavy chain regulates p53-mediated transcription

Ohmori, Kitaro; Endo, Y; Yoshida, Yusuke; Ohata, Hirokazu; Taya, Yoichi; Enari, Masato

doi:10.1038/sj.onc.1210854

Cited by 24 publications

(31 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…both Western blotting and confocal laser microscopy; (ii) Cep97 is known to be required for the recruitment of CP110, a protein that regulates centrosomal duplication (17); (iii) in BCC, CD9 knockdown resulted in multipolar mitoses and polyploidy, phenocopying the effects described by others in BCC upon Cep97 or CP110 knockdown (17); (iv) depletion of clathrin, a protein involved in receptormediated endocytosis, with a biologically important nuclear pool (20), reportedly impaired mitotic spindle stability and cytokinesis (21); (v) Cp190 and CP60, other important centrosomal proteins, reportedly translocated from the nucleus to the centrosome during different phases of the cell cycle (22,23). CD9 is reportedly involved in cell fusion (1), which may lead to formation of multipolar spindles and polynucleation.…”

Section: Discussionmentioning

confidence: 99%

The Nuclear Pool of Tetraspanin CD9 Contributes to Mitotic Processes in Human Breast Carcinoma

Rappa

Green

Lorico

2014

Molecular Cancer Research

View full text Add to dashboard Cite

Tetraspanin-29 (CD9) is an integral membrane protein involved in several fundamental cell processes and in cancer metastasis. Here, characterization of a panel of breast cancer cells revealed a nuclear pool of CD9, not present in normal human mammary epithelial cells. Antibody binding to surface CD9 of breast cancer cells resulted in increased nuclear CD9 fluorescence. CD9 was also found, along with a plasma membrane-associated pool, in the nuclei of all primary ductal breast carcinoma patient specimens analyzed. In all patients, about 40% of the total CD9 cellular fluorescence was nuclear. CD9 colocalized at the nuclear level with CEP97, a protein implicated in centrosome function, and with the IGSF8, an established CD9 partner in the plasma membrane. Co-immunoprecipitation of CEP97 and IGSF8 with CD9 was shown in nuclear extracts from breast cancer cells expressing a CD9-GFP fusion protein. However, by fluorescence resonance energy transfer (FRET) analysis, no direct binding of CD9 with either protein was observed, suggesting that CD9 is part of a larger nuclear protein complex. CD9 depletion or exposure of parental breast cancer cells to anti-CD9 mAb resulted in polynucleation and multipolar mitoses. These data indicate that the nuclear CD9 pool has an important role in the mitotic process.

show abstract

Section: Discussionmentioning

confidence: 99%

The Nuclear Pool of Tetraspanin CD9 Contributes to Mitotic Processes in Human Breast Carcinoma

Rappa

Green

Lorico

2014

Molecular Cancer Research

View full text Add to dashboard Cite

show abstract

“…About 5% of CHC17 was found by nuclear fractionation and immunoelectron microscopy to be in nuclear spaces (56). Luciferase-based reporter assays indicate that CHC17 nuclear localization is increased by artificially deleting the trimerization domain (57). However, the proposal that clathrin must be monomeric to help activate p53 has been controversial because there is no defined mechanism to alter clathrin structure.…”

Section: Clathrin Detrimerization and Nuclear Localizationmentioning

confidence: 99%

“…There are reports that clathrin is involved in activating p53 by entering the nucleus to present histone acetyltransferase p300 to p53 (56,57). However, this novel cancer connection is debatable because luciferase-based detection assays show that the functional form of CHC17 is the monomer that must somehow localize to the nucleus.…”

Section: Clathrin and P53 Activationmentioning

confidence: 99%

Novel clathrin activity: developments in health and disease

Ybe

2014

Biomolecular Concepts

View full text Add to dashboard Cite

Clathrin self-assembles into a coat around vesicles filled with cargo such as nutrients, hormones, and proteins destined for degradation. Recent developments indicate clathrin is not a specialist, but is involved in different processes relevant to health and disease. Clathrin is used to strengthen centrosomes and mitotic spindles essential for chromosome segregation in cell division. In Wnt signaling, clathrin is a component of signalosomes on the plasma membrane needed to produce functional Wnt receptors. In glucose metabolism, a muscle-specific isoform, CHC22 clathrin, is key to the formation of storage compartments for GLUT4 receptor, and CHC22 dysfunction has been tied to type 2 diabetes. The activity of clathrin to self-assemble and to work with huntingtin-interacting proteins to organize actin is exploited by Listeria and enteropathic Escherichia coli in their infection pathways. Finally, there is an important connection between clathrin and human malignancies. Clathrin is argued to help transactivate tumor suppressor p53 that controls specific genes in DNA repair and apoptosis. However, this is debatable because trimeric clathrin must be made monomeric. To get insight on how the clathrin structure could be converted, the crystal structure of the trimerization domain is used in the development of the detrimerization switch hypothesis. This novel hypothesis will be relevant if connections continue to be found between CHC17 and p53 anti-cancer activity in the nucleus.

show abstract

“…The exogenous expression of CHC17 increases the transactivation of p53-responsive promoters ( p53AIP1, P21 waf1 , p53R2, and Noxa), whereas RNAi silencing reduces p53 transcriptional activity (Enari et al 2006). There are data showing that CHC17 recruits histone acetyltransferase p300 to p53 to promote p53-mediated transcription (Enari et al 2006;Ohmori et al 2008). Nuclear fractionation and immuno-electron microscopy studies detect a small fraction ( 5%) of CHC17 in the nucleus (Enari et al 2006).…”

Section: Transcriptional Function and Oncogenesismentioning

confidence: 99%

Unconventional Functions for Clathrin, ESCRTs, and Other Endocytic Regulators in the Cytoskeleton, Cell Cycle, Nucleus, and Beyond: Links to Human Disease

Brodsky

Sosa

Ybe

et al. 2014

Cold Spring Harbor Perspectives in Biology

View full text Add to dashboard Cite

The roles of clathrin, its regulators, and the ESCRT (endosomal sorting complex required for transport) proteins are well defined in endocytosis. These proteins can also participate in intracellular pathways that are independent of endocytosis and even independent of the membrane trafficking function of these proteins. These nonendocytic functions involve unconventional biochemical interactions for some endocytic regulators, but can also exploit known interactions for nonendocytic functions. The molecular basis for the involvement of endocytic regulators in unconventional functions that influence the cytoskeleton, cell cycle, signaling, and gene regulation are described here. Through these additional functions, endocytic regulators participate in pathways that affect infection, glucose metabolism, development, and cellular transformation, expanding their significance in human health and disease.

show abstract

Monomeric but not trimeric clathrin heavy chain regulates p53-mediated transcription

Cited by 24 publications

References 43 publications

The Nuclear Pool of Tetraspanin CD9 Contributes to Mitotic Processes in Human Breast Carcinoma

The Nuclear Pool of Tetraspanin CD9 Contributes to Mitotic Processes in Human Breast Carcinoma

Novel clathrin activity: developments in health and disease

Unconventional Functions for Clathrin, ESCRTs, and Other Endocytic Regulators in the Cytoskeleton, Cell Cycle, Nucleus, and Beyond: Links to Human Disease

Contact Info

Product

Resources

About