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SHP-2 and PTP-pest induction during Rb-E2F associated apoptosis

Cellular & Molecular Biology Letters volume 17, pages 422–432 (2012)Cite this article

Abstract

Apoptosis is intimately connected to cell cycle regulation via the Retinoblastoma (Rb)-E2F pathway and thereby serves an essential role in tumor suppression by eliminating aberrant hyperproliferative cells. Upon loss of Rb activity, an apoptotic response can be elicited through both p53-dependent and p53-independent mechanisms. While much of this apoptotic response has been attributed to the p19ARF/p53 pathway, increasing evidence has supported the role of protein tyrosine phosphatases (PTPs) in contributing to the initiation of the Rb-E2F-associated apoptotic response. One protein tyrosine phosphatase, PTP-1B, which is induced by the Rb-E2F pathway, has been shown to contribute to a p53-independent apoptotic pathway by inactivating focal adhesion kinase. This report identifies two additional PTPs, SHP-2 and PTP-PEST, that are also directly activated by the Rb-E2F pathway and which can contribute to signal transduction during p53-independent apoptosis.

Abbreviations

4OHT:

4-hydroxytamoxifen

dnE2F:

dominant negative mutant of E2F-1

ER:

estrogen receptor

FAK:

focal adhesion kinase

PTP:

protein tyrosine phosphatase

PTP-PEST:

protein tyrosine phosphatase rich in proline, glutamic acid/aspartic acid, and serine/threonine residues

Rb:

retinoblastoma protein

SHP-2:

SH2 domain-containing tyrosine phosphatase

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Authors and Affiliations

  1. Department of Biology, The University of Texas-Pan American, Edinburg, TX, USA

    Liza D. Morales, Karina Pena & Jonathan H. Lieman

  2. Department of Pharmacology, University of Texas Health Science Center at San Antonio, Edinburg, TX, USA

    Dae Joon Kim

  3. Edinburg Regional Academic Health Center, Medical Research Division, University of Texas Health Science Center at San Antonio, Edinburg, TX, USA

    Liza D. Morales & Dae Joon Kim

Authors
  1. Liza D. Morales
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  2. Karina Pena
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  3. Dae Joon Kim
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  4. Jonathan H. Lieman
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Correspondence to Jonathan H. Lieman.

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Morales, L.D., Pena, K., Kim, D.J. et al. SHP-2 and PTP-pest induction during Rb-E2F associated apoptosis. Cell Mol Biol Lett 17, 422–432 (2012). https://doi.org/10.2478/s11658-012-0020-9

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