Protein patterns of the nuclear matrix in differently proliferating and malignant cells

Kuzmina, Svetlana; Buldyaeva, T. V.; Akopov, S. B.; Zbarsky, I. B.

doi:10.1007/bf00240618

Cited by 11 publications

(7 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As shown in Fig. 5B, the antibody anti-lamin B, one of the major components of nuclear matrix (25), was used to verify the effectiveness of nuclear matrix fractionation (top panel). Lamin B was detected mainly in the nuclear matrix fraction in both uninduced and TPA-treated BCBL-1 cells.…”

Section: Resultsmentioning

confidence: 99%

Identification and Characterization of the Product Encoded by ORF69 of Kaposi's Sarcoma-Associated Herpesvirus

Santarelli

Farina²,

Granato

et al. 2008

J Virol

View full text Add to dashboard Cite

We report the identification and characterization of p33, the product of Kaposi's sarcoma-associated herpesvirus (KSHV) open reading frame 69 (ORF69), a positional homolog of the conserved herpesvirus protein UL31. p33 is expressed upon induction of viral lytic cycle with early kinetics. Immunofluorescence analysis revealed that in infected cell lines, the protein is localized in the nucleus, both in dotted spots and along the nuclear membrane. Nuclear fractionation experiments showed that p33 partitions with the nuclear matrix, and both immunoblotting of purified virions and immunoelectron microscopy indicated that the novel protein is not a component of the mature virus. Following ectopic expression in KSHV-negative cells, the protein was never associated with the nuclear membrane, suggesting that p33 needs to interact with additional viral proteins to reach the nuclear rim. In fact, after cotransfection with the ORF67 gene, the KSHV positional homolog of UL34, the p33 intranuclear signal changed and the two proteins colocalized on the nuclear membrane. A similar result was obtained when ORF69 was cotransfected with BFRF1, the Epstein-Barr virus (EBV) positional homolog of UL34 and ORF67. Finally, upon cotransfection, ORF69 significantly increased nuclear membrane reduplications induced by BFRF1. The above results indicate that KSHV p33 shares many similarities with its EBV homolog BFLF2 and suggest that functional cross-complementation is possible between members of the gammaherpesvirus subfamily.A number of proteins are conserved among all herpesviruses and are designated "core proteins." Among these, UL34 and UL31 protein family members have been studied extensively in the alphaherpesviruses herpes simplex virus type 1 (HSV-1) (54, 41), HSV-2 (53), pseudorabies virus (15), and equine herpesvirus 1 (EHV) (37) and in the betaherpesviruses human cytomegalovirus (CMV) (10) and mouse CMV (35, 47). For gammaherpesviruses, we initially identified and characterized the product of the Epstein-Barr virus (EBV) homolog of UL34, BFRF1 (12, 13), which has subsequently been shown to interact with the UL31 homolog BFLF2 (16,26) and to play an essential role in viral envelopment at the nuclear membrane (14).In all cases analyzed, UL34 and UL31 formed a complex at the inner nuclear membrane referred to as the nuclear egress complex (NEC), which is essential for viral egress (reviewed in reference 31), by interacting with viral (22, 44) and cellular kinases (35, 39) or with nuclear lamins (3,16,34,43). These interactions contribute to the dismantling of the rigid nuclear lamina (35) and facilitate access of nucleocapids to the nuclear membrane for primary envelopment.Very little is known of the intracellular viral maturation pathway of the second human gammaherpesvirus, Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV-8), a lymphotropic herpesvirus detected in biopsies of all clinical and epidemiological forms of Kaposi's sarcoma and also linked to lymphoproliferative disorders, such as ...

show abstract

Section: Resultsmentioning

confidence: 99%

Identification and Characterization of the Product Encoded by ORF69 of Kaposi's Sarcoma-Associated Herpesvirus

Santarelli

Farina²,

Granato

et al. 2008

J Virol

View full text Add to dashboard Cite

show abstract

“…Third, because lamins sequester transcription regulators such as cFos, Jun and pRb (Markiewicz et al, 2002;Ivorra et al, 2006) and contribute to their activity through regulating their phosphorylation state (Van Berlo et al, 2005), altering the lamin polymer could directly affect commitment to cell division. In support of this view, B-type lamins tend to keep being expressed in tumors while A-type lamins are often downregulated (Kuzmina et al, 1984;Kaufmann et al, 1991;Venables et al, 2001;Agrelo et al, 2005). Because A-type lamins reflect later stages of differentiation (Rober et al, 1989), their loss had been thought to reflect the return of tumor cells to a retrodifferentiated or de-differentiated state with higher proliferative potential (Kuzmina et al, 1984).…”

Section: Lamins In Nuclear Mechanics Regulation Nuclear Size Control ...mentioning

confidence: 99%

Nuclear size rectification: A potential new therapeutic approach to reduce metastasis in cancer

Schirmer

Latonen

Tollis

2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Research on metastasis has recently regained considerable interest with the hope that single cell technologies might reveal the most critical changes that support tumor spread. However, it is possible that part of the answer has been visible through the microscope for close to 200 years. Changes in nuclear size characteristically occur in many cancer types when the cells metastasize. This was initially discarded as contributing to the metastatic spread because, depending on tumor types, both increases and decreases in nuclear size could correlate with increased metastasis. However, recent work on nuclear mechanics and the connectivity between chromatin, the nucleoskeleton, and the cytoskeleton indicate that changes in this connectivity can have profound impacts on cell mobility and invasiveness. Critically, a recent study found that reversing tumor type-dependent nuclear size changes correlated with reduced cell migration and invasion. Accordingly, it seems appropriate to now revisit possible contributory roles of nuclear size changes to metastasis.

show abstract

“…The general tendency observed is that B-type lamins continue to be expressed in tumors while A-type lamins are downregulated (62)(63)(64). Because A-type lamins appear later in development, this led to the idea that their loss reflects retro-differentiation or de-differentiation and so might drive or at least reflect the return to a more proliferative and undifferentiated state (65). However, research in this direction was dropped when it was observed that for some cancer types such as colorectal cancer the more metastatic tumors had increased A-type lamin levels (66).…”

Section: Laminsmentioning

confidence: 99%

Breaking the scale: how disrupting the karyoplasmic ratio gives cancer cells an advantage for metastatic invasion

Rizzotto

Schirmer

2017

Biochemical Society Transactions

View full text Add to dashboard Cite

Nuclear size normally scales with the size of the cell, but in cancer this 'karyoplasmic ratio' is disrupted. This is particularly so in more metastatic tumors where changes in the karyoplasmic ratio are used in both diagnosis and prognosis for several tumor types. However, the direction of nuclear size changes differs for particular tumor types: for example in breast cancer, larger nuclear size correlates with increased metastasis, while for lung cancer smaller nuclear size correlates with increased metastasis. Thus, there must be tissue-specific drivers of the nuclear size changes, but proteins thus far linked to nuclear size regulation are widely expressed. Notably, for these tumor types, ploidy changes have been excluded as the basis for nuclear size changes, and so, the increased metastasis is more likely to have a basis in the nuclear morphology change itself. We review what is known about nuclear size regulation and postulate how such nuclear size changes can increase metastasis and why the directionality can differ for particular tumor types.

show abstract

Protein patterns of the nuclear matrix in differently proliferating and malignant cells

Cited by 11 publications

References 8 publications

Identification and Characterization of the Product Encoded by ORF69 of Kaposi's Sarcoma-Associated Herpesvirus

Identification and Characterization of the Product Encoded by ORF69 of Kaposi's Sarcoma-Associated Herpesvirus

Nuclear size rectification: A potential new therapeutic approach to reduce metastasis in cancer

Breaking the scale: how disrupting the karyoplasmic ratio gives cancer cells an advantage for metastatic invasion

Contact Info

Product

Resources

About