TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain

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R-HSA-6804115
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Pathway
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Homo sapiens
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BTG2 is induced by TP53, leading to cessation of cellular proliferation (Rouault et al. 1996, Duriez et al. 2002). BTG2 binds to the CCR4-NOT complex and promotes mRNA deadenylation activity of this complex. Interaction between BTG2 and CCR4-NOT is needed for the antiproliferative activity of BTG2, but the underlying mechanism has not been elucidated (Rouault et al. 1998, Mauxion et al. 2008, Horiuchi et al. 2009, Doidge et al. 2012, Ezzeddine et al. 2012). Two polo-like kinases, PLK2 and PLK3, are direct transcriptional targets of TP53. TP53-mediated induction of PLK2 may be important for prevention of mitotic catastrophe after spindle damage (Burns et al. 2003). PLK2 is involved in the regulation of centrosome duplication through phosphorylation of centrosome-related proteins CENPJ (Chang et al. 2010) and NPM1 (Krause and Hoffmann 2010). PLK2 is frequently transcriptionally silenced through promoter methylation in B-cell malignancies (Syed et al. 2006). Induction of PLK3 transcription by TP53 (Jen and Cheung 2005) may be important for coordination of M phase events through PLK3-mediated nuclear accumulation of CDC25C (Bahassi et al. 2004). RGCC is induced by TP53 and implicated in cell cycle regulation, possibly through its association with PLK1 (Saigusa et al. 2007). PLAGL1 (ZAC1) is a zinc finger protein directly transcriptionally induced by TP53 (Rozenfeld-Granot et al. 2002). PLAGL1 expression is frequently lost in cancer (Varrault et al. 1998) and PLAGL1 has been implicated in both cell cycle arrest and apoptosis (Spengler et al. 1997), but its mechanism of action remains unknown.

Literature References
PubMed ID Title Journal Year
14968113 Cdc25C phosphorylation on serine 191 by Plk3 promotes its nuclear translocation

Myer, DL, Bahassi, el M, Stambrook, PJ, Hennigan, RF

Oncogene 2004
19276069 Structural basis for the antiproliferative activity of the Tob-hCaf1 complex

Horiuchi, M, Inagaki, F, Muroya, N, Takeuchi, K, Kawamura-Tsuzuku, J, Nakamura, T, Suzuki, T, Noda, N, Yamamoto, T, Takahasi, K

J. Biol. Chem. 2009
9671765 hZAC encodes a zinc finger protein with antiproliferative properties and maps to a chromosomal region frequently lost in cancer

Hoffmann, A, Pantaloni, C, Bilanges, B, Journot, L, Apiou, F, Ciani, E, Varrault, A, Spengler, D, Bockaert, J

Proc. Natl. Acad. Sci. U.S.A. 1998
11896574 A positive feedback mechanism in the transcriptional activation of Apaf-1 by p53 and the coactivator Zac-1

Amariglio, N, Kannan, K, Rechavi, G, Toren, A, Givol, D, Krishnamurthy, J, Rozenfeld-Granot, G

Oncogene 2002
9712883 Interaction of BTG1 and p53-regulated BTG2 gene products with mCaf1, the murine homolog of a component of the yeast CCR4 transcriptional regulatory complex

Birot, AM, Corbo, L, Berthet, C, Billaud, M, Rouault, JP, Magaud, JP, Prévôt, D

J. Biol. Chem. 1998
16140933 Identification of novel p53 target genes in ionizing radiation response

Jen, KY, Cheung, VG

Cancer Res. 2005
18337750 The BTG2 protein is a general activator of mRNA deadenylation

Séraphin, B, Mauxion, F, Faux, C

EMBO J. 2008
8944033 Identification of BTG2, an antiproliferative p53-dependent component of the DNA damage cellular response pathway

Puisieux, A, Savatier, P, Pain, B, Guillot, C, Falette, N, Ozturk, M, Moyret-Lalle, C, Rimokh, R, Rouault, JP, Magaud, JP, Guéhenneux, F, Samarut, C, Berger, R, Wang, Q, Shaw, P, Berthet, C, Samarut, J

Nat. Genet. 1996
16160013 Transcriptional silencing of Polo-like kinase 2 (SNK/PLK2) is a frequent event in B-cell malignancies

Karran, L, Hoffmann, I, Smith, P, Sullivan, A, Griffin, B, Allday, M, Spender, LC, Syed, N, Dyer, M, Crawford, D, O'Nions, J, Farrell, PJ, Crook, T

Blood 2006
20531387 PLK2 phosphorylation is critical for CPAP function in procentriole formation during the centrosome cycle

Rhee, K, Chang, J, Hoffmann, I, Cizmecioglu, O

EMBO J. 2010
22252318 Evidence providing new insights into TOB-promoted deadenylation and supporting a link between TOB's deadenylation-enhancing and antiproliferative activities

Chen, CY, Ezzeddine, N, Shyu, AB

Mol. Cell. Biol. 2012
17146433 RGC32, a novel p53-inducible gene, is located on centrosomes during mitosis and results in G2/M arrest

Saigusa, K, Tanikawa, C, Inazawa, J, Aoyagi, M, Nakamura, Y, Ohno, K, Imoto, I

Oncogene 2007
23236473 The anti-proliferative activity of BTG/TOB proteins is mediated via the Caf1a (CNOT7) and Caf1b (CNOT8) deadenylase subunits of the Ccr4-not complex

Aslam, A, Mittal, S, Doidge, R, Winkler, GS

PLoS ONE 2012
11814693 The human BTG2/TIS21/PC3 gene: genomic structure, transcriptional regulation and evaluation as a candidate tumor suppressor gene

Audoynaud, C, Puisieux, A, Moyret-Lalle, C, Bensaad, K, Wang, Q, Soussi, T, Falette, N, Duriez, C, Courtois, S

Gene 2002
12897130 Silencing of the novel p53 target gene Snk/Plk2 leads to mitotic catastrophe in paclitaxel (taxol)-exposed cells

Dicker, DT, Scata, KA, Fei, P, Burns, TF, El-Deiry, WS

Mol. Cell. Biol. 2003
20352051 Polo-like kinase 2-dependent phosphorylation of NPM/B23 on serine 4 triggers centriole duplication

Hoffmann, I, Krause, A

PLoS ONE 2010
9184226 Regulation of apoptosis and cell cycle arrest by Zac1, a novel zinc finger protein expressed in the pituitary gland and the brain

Hoffmann, A, Pantaloni, C, Houssami, S, Villalba, M, Journot, L, Spengler, D, Bockaert, J

EMBO J. 1997
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