A regulatory mechanism involving TBP-1/Tat-Binding Protein 1 and Akt/PKB in the control of cell proliferation
Authors: Luisa Festa
Fabio Tolino
Vittorio de Franciscis
Girolama La Mantia
Pia Ragno
Luca Sisto
Daniela Alfano
Viola Calabrò
Luca Bellucci
Maria Sepe
Alessandra Pollice
Journal: PLoS ONE (2011)
Discipline: Multidisciplinary
Keywords: TBP-1; HIV-1-Tat; transcription; proteasome; cell proliferation
Affiliations: Dipartimento di Biologia Strutturale e Funzionale, Università di Napoli Federico II, Naples, Italy.

Abstract:  TBP-1 /Tat-Binding Protein 1 (also named Rpt-5, S6a or PSMC3) is a multifunctional protein, originally identified as a regulator of HIV-1-Tat mediated transcription. It is an AAA-ATPase component of the 19S regulative subunit of the proteasome and, as other members of this protein family, fulfils different cellular functions including proteolysis and transcriptional regulation. We and others reported that over expression of TBP-1 diminishes cell proliferation in different cellular contexts with mechanisms yet to be defined. Accordingly, we demonstrated that TBP-1 binds to and stabilizes the p14ARF oncosuppressor increasing its anti-oncogenic functions. However, TBP-1 restrains cell proliferation also in the absence of ARF, raising the question of what are the molecular pathways involved. Herein we demonstrate that stable knock-down of TBP-1 in human immortalized fibroblasts increases cell proliferation, migration and resistance to apoptosis induced by serum deprivation. We observe that TBP-1 silencing causes activation of the Akt/PKB kinase and that in turn TBP-1, itself, is a downstream target of Akt/PKB. Moreover, MDM2, a known Akt target, plays a major role in this regulation. Altogether, our data suggest the existence of a negative feedback loop involving Akt/PKB that might act as a sensor to modulate TBP-1 levels in proliferating cells. 

Retracted: Yes

PubPeer comments:
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 ![file] , 
 2019 retraction. https: journals.plos.org plosone article?id=10.1371 journal.pone.0222287 Following publication of this article [1], the following concerns were raised: Fig 1A actin panel lane 4 appears similar to lane 7; Fig 5B actin panels look similar to each other; Fig 5B upper pAkt panel, lanes 1, 5, and 6 appear to have a background different to the other lanes; Fig 5F Akt panel lanes 1u20136 appear similar to Fig 6B C8 panel lanes 2u20137 and to Fig 6E Akt panel lanes 1u20136; Fig 6A C8 lanes 2, 3 appear similar to lanes 5, 6 and there are vertical discontinuities after lane 4; Fig 6B pAkt panel contains background discontinuities across lanes 1u20134; Fig 6B TBP-1 panel contains background discontinuities after lane 4 such that the background differs between lanes 1u20134 and 5u20137; Fig 6C pAkt panel contains background discontinuities between lanes 2 and 3. The authors provided data underlying replication experiments that confirm some of the results presented in the article. However, owing to the length of time since the experiments were carried out, none of the original underlying data are available to resolve the concerns raised. In light of the unresolved concerns that question the validity of the studyu2019s findings, the PLOS ONE Editors retract the article. AP notified the journal office that DA, PR, VC, VdF, GLM, AP agree to the retraction, but are confident in the findings and stand by the published results. MS, LF, FT, LB, LS did not respond to the retraction notification. Reference 1.Sepe M, Festa L, Tolino F, Bellucci L, Sisto L, Alfano D, et al. (2011) A Regulatory Mechanism Involving TBP-1 Tat-Binding Protein 1 and Akt PKB in the Control of Cell Proliferation. PLoS ONE 6(10): e22800. https: doi.org 10.1371 journal.pone.0022800 pmid:21991300 , 
 Members of this author group have a number of threads with similar concerns, many of which have not been addressed by the authors or journals. https: pubpeer.com search?q=authors%3A%28%22Girolama+La+Mantia%22%29 https: pubpeer.com search?q=authors%3A%22Viola+Calabr%C3%B2%22 https: pubpeer.com search?q=authors%3A%22Alessandra+Pollice%22 Note: These lists may have duplicate papers, as well as false positives and false negatives. This is not an accusation of misconduct, and author replies are welcome. ,