Pontin is localized in nucleolar fibrillar centers

Cvačková, Zuzana; Albring, Kai Frederik; Koberna, Karel; Ligasová, Anna; Huber, Otmar; Raška, Ivan; Staněk, David

doi:10.1007/s00412-008-0170-8

Cited by 10 publications

(9 citation statements)

References 36 publications

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“…It has been also reported that pre-rRNA processing is regulated by R2TP complex [7]. Interestingly, mTOR, PIH1D1, and another component of R2TP complex, Rvb1 (pontin in human) are localized in nucleoli [34][35][36]. PIH1D1 is known to be an unstable protein [7], and we have reported that PIH1D1 is stabilized by another component of R2TP complex, Tah1 (RPAP3 in human) [15].…”

Section: Discussionmentioning

confidence: 62%

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PIH1D1 interacts with mTOR complex 1 and enhances ribosome RNA transcription

et al. 2013

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Edited by Gianni CesareniKeywords: Monad PIH1D1 R2TP Breast cancer mTOR Ribosome a b s t r a c t PIH1D1 is the defining component of the R2TP complex. Recently, R2TP has been reported to stabilize mTOR (mammalian target of rapamycin), an important regulator of cell growth and protein synthesis. Two complexes of mTOR, mTORC1 and mTORC2, have been identified. We demonstrate that immunoprecipitation (IP) of PIH1D1 results in the co-IP of Raptor (mTORC1 specific), but not Rictor (mTORC2 specific), and that knockdown of PIH1D1 decreases mTORC1 assembly, S6 kinase phosphorylation (indicator of mTORC1 activity), and rRNA transcription without affecting mTORC2 in human breast cancer MCF-7 cells. In addition, we provide evidence that PIH1D1 is overexpressed in various breast cancer cell lines. These findings collectively suggest that PIH1D1 may have an important role in mTORC1 regulation in breast cancers. Structured summary of protein interactions:mTOR physically interacts with PIH1D1 and Raptor by anti tag coimmunoprecipitation (View interaction) Rictor physically interacts with mTOR and Tel2 by anti bait coimmunoprecipitation (View interaction) Raptor physically interacts with Tel2, PIH1D1 and mTOR by anti bait coimmunoprecipitation (View interaction) PIH1D1 physically interacts with mTOR and Raptor by anti bait coimmunoprecipitation (View interaction)

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Section: Discussionmentioning

confidence: 62%

“…It has been also reported that pre‐rRNA processing is regulated by R2TP complex [7]. Interestingly, mTOR, PIH1D1, and another component of R2TP complex, Rvb1 (pontin in human) are localized in nucleoli [34–36].…”

Section: Discussionmentioning

confidence: 95%

PIH1D1 interacts with mTOR complex 1 and enhances ribosome RNA transcription

et al. 2013

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“…On the other hand, Pontin and Reptin can act as activators of MYC-mediated transcription. Within the nucleolus, an interaction of Pontin and MYC at the rRNA promoter was observed (Figure 5A ), though the function and the mechanistic aspects of this interaction are still unclear (Cvackova et al, 2008 ). Recent findings suggested that rRNA transcription might also be regulated by the R2TP complex indirectly through its interactions with mTORC1 (Kamano et al, 2013 ).…”

Section: Role Of Pontin/reptin In Specific Cellular Pathwaysmentioning

confidence: 99%

The Role of Pontin and Reptin in Cellular Physiology and Cancer Etiology

Mao

Houry

2017

Front. Mol. Biosci.

104

101

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Pontin (RUVBL1, TIP49, TIP49a, Rvb1) and Reptin (RUVBL2, TIP48, TIP49b, Rvb2) are highly conserved ATPases of the AAA+ (ATPases Associated with various cellular Activities) superfamily and are involved in various cellular processes that are important for oncogenesis. First identified as being upregulated in hepatocellular carcinoma and colorectal cancer, their overexpression has since been shown in multiple cancer types such as breast, lung, gastric, esophageal, pancreatic, kidney, bladder as well as lymphatic, and leukemic cancers. However, their exact functions are still quite unknown as they interact with many molecular complexes with vastly different downstream effectors. Within the nucleus, Pontin and Reptin participate in the TIP60 and INO80 complexes important for chromatin remodeling. Although not transcription factors themselves, Pontin and Reptin modulate the transcriptional activities of bona fide proto-oncogenes such as MYC and β-catenin. They associate with proteins involved in DNA damage repair such as PIKK complexes as well as with the core complex of Fanconi anemia pathway. They have also been shown to be important for cell cycle progression, being involved in assembly of telomerase, mitotic spindle, RNA polymerase II, and snoRNPs. When the two ATPases localize to the cytoplasm, they were reported to promote cancer cell invasion and metastasis. Due to their various roles in carcinogenesis, it is not surprising that Pontin and Reptin are proving to be important biomarkers for diagnosis and prognosis of various cancers. They are also current targets for the development of new therapeutic anticancer drugs.

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“…Albring and Huber previously reported that within the nucleolus, Pontin associates with RNA polymerase I and forms a complex at regulatory sites of ribosomal RNA transcription with c-Myc (14). They now report that the estrogen receptor forms complexes with Pontin or Reptin, or both, at regulatory cis elements in a gene-specific manner.…”

Section: Nuclear Functions: Transcription and Chromatin Remodelingmentioning

confidence: 99%

The Emergence of the Conserved AAA+ ATPases Pontin and Reptin on the Signaling Landscape Meeting Information: The First International Workshop on Pontin (RUVBL1) and Reptin (RUVBL2) took place at the European Institute for Chemistry and Biology in Pessac, France, 16 to 19 October 2012.

et al. 2013

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Pontin (also known as RUVBL1 and RVB1) and Reptin (also called RUVBL2 and RVB2) are related members of the large AAA+ (adenosine triphosphatase associated with diverse cellular activities) superfamily of conserved proteins. Various cellular functions depend on Pontin and Reptin, mostly because of their functions in the assembly of protein complexes that play a role in the regulation of cellular energetic metabolism, transcription, chromatin remodeling, and the DNA damage response. Little is known, though, about the interconnections between these multiple functions, how the relevant signaling pathways are regulated, whether the interconnections are affected in human disease, and whether components of these pathways are suitable targets for therapeutic intervention. The First International Workshop on Pontin (RUVBL1) and Reptin (RUVBL2), held between 16 and 19 October 2012, discussed the nature of the oligomeric organization of these proteins, their structures, their roles as partners in various protein complexes, and their involvement in cellular regulation, signaling, and pathophysiology, as well as their potential for therapeutic targeting. A major outcome of the meeting was a general consensus that most functions of Pontin and Reptin are related to their roles as chaperones or adaptor proteins that are important for the assembly and function of large signaling protein complexes.

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Pontin is localized in nucleolar fibrillar centers

Cited by 10 publications

References 36 publications

PIH1D1 interacts with mTOR complex 1 and enhances ribosome RNA transcription

PIH1D1 interacts with mTOR complex 1 and enhances ribosome RNA transcription

The Role of Pontin and Reptin in Cellular Physiology and Cancer Etiology

The Emergence of the Conserved AAA+ ATPases Pontin and Reptin on the Signaling Landscape Meeting Information: The First International Workshop on Pontin (RUVBL1) and Reptin (RUVBL2) took place at the European Institute for Chemistry and Biology in Pessac, France, 16 to 19 October 2012.

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