p16

p16, conosciuta anche come INK4a, è una proteina codificata dal gene CDKN2A, il quale codifica anche per la proteina p14 (o p14arf).

Funzione

p16 appartiene alla famiglia delle CDKI, proteine che hanno la funzione di inibire l'azione delle chinasi dipendenti da ciclina (CDK), e quindi sono in grado di bloccare il ciclo cellulare ed impedire la mitosi. Per tali funzioni il gene per questa proteina è definito un oncosoppressore ed è infatti ritrovato mutato o down-regolato in vari fenomeni tumorali tra cui il cancro al fegato. Poiché tra i target della proteina compare CDK4, il quale è un inibitore della proteina RB, questa proteina è in grado di incrementare l'attività della proteina e fa parte della via biochimica del RB. Inibisce la progressione del ciclo cellulare bloccandolo in fase Gap 1.

Interazioni

Sembra che il gene di p16 interagisca con SERTAD1,^[1]^[2] CCNG1,^[3] DAXX,^[4] P53,^[5]^[6]^[7] E4F1,^[6] CDK4,^[1]^[2]^[8]^[9]^[10]^[11] CDK6,^[9]^[12]^[13] Mdm2,^[4]^[5]^[7]^[14]^[15] RPL11^[5] e PPP1R9B.^[16]

Note

^ ^a ^b Junan Li, , Tsai Ming-Daw, Muscarella Peter, Ming-Daw Tsai e Peter Muscarella, The nuclear protein p34SEI-1 regulates the kinase activity of cyclin-dependent kinase 4 in a concentration-dependent manner, in Biochemistry, vol. 43, n. 14, United States, aprile 2004, pp. 4394–9, DOI:10.1021/bi035601s, ISSN 0006-2960 (WC · ACNP), PMID 15065884.
^ ^a ^b M Sugimoto, Ohtani N, Hampson L, Hampson I N, Shimamoto A, Furuichi Y, Okumura K, Niwa S e Taya Y, Regulation of CDK4 activity by a novel CDK4-binding protein, p34SEI-1, in Genes Dev., vol. 13, n. 22, UNITED STATES, novembre 1999, pp. 3027–33, DOI:10.1101/gad.13.22.3027, ISSN 0890-9369 (WC · ACNP), PMC 317153, PMID 10580009.
^ Lili Zhao, Winckler Sarah, Korgaonkar Chandrashekhar, Tompkins Van, Horne Mary C, , Quelle Dawn E e DE Quelle, Cyclin G1 has growth inhibitory activity linked to the ARF-Mdm2-p53 and pRb tumor suppressor pathways, in Mol. Cancer Res., vol. 1, n. 3, United States, Jan. 2003, pp. 195–206, ISSN 1541-7786 (WC · ACNP), PMID 12556559.
^ ^a ^b Stacey M Ivanchuk, , Rutka James T e James T. Rutka, p14ARF interacts with DAXX: effects on HDM2 and p53, in Cell Cycle, vol. 7, n. 12, United States, giugno 2008, pp. 1836–50, DOI:10.4161/cc.7.12.6025, PMID 18583933.
^ ^a ^b ^c Yanping Zhang, Bhat Krishna, Jin Aiwen, Allio Theresa, Burkhart William A, , Xiong Yue e Y. Xiong, Ribosomal Protein L11 Negatively Regulates Oncoprotein MDM2 and Mediates a p53-Dependent Ribosomal-Stress Checkpoint Pathway, in Mol. Cell. Biol., vol. 23, n. 23, United States, dicembre 2003, pp. 8902–12, DOI:10.1128/MCB.23.23.8902-8912.2003, ISSN 0270-7306 (WC · ACNP), PMC 262682, PMID 14612427.
^ ^a ^b Helen Rizos, Badhwar Prerna, Woodruff Sarah, Becker Therese M, Rooney Robert J, , Kefford Richard F e RF Kefford, Association of p14ARF with the p120E4F transcriptional repressor enhances cell cycle inhibition, in J. Biol. Chem., vol. 278, n. 7, United States, febbraio 2003, pp. 4981–9, DOI:10.1074/jbc.M210978200, ISSN 0021-9258 (WC · ACNP), PMID 12446718.
^ ^a ^b Y Zhang, , Yarbrough W G e Wendell G Yarbrough, ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways, in Cell, vol. 92, n. 6, UNITED STATES, marzo 1998, pp. 725–34, DOI:10.1016/S0092-8674(00)81401-4, ISSN 0092-8674 (WC · ACNP), PMID 9529249.
^ Rob M Ewing, Elisma Fred, Li Hongyan, Taylor Paul, Climie Shane, McBroom-Cerajewski Linda, Robinson Mark D, Connor Liam e Li Michael, Large-scale mapping of human protein–protein interactions by mass spectrometry, in Mol. Syst. Biol., vol. 3, n. 1, England, 2007, pp. 89, DOI:10.1038/msb4100134, PMC 1847948, PMID 17353931.
^ ^a ^b R Fåhraeus, Ball K L, Laín S, , Lane D P e David P. Lane, Inhibition of pRb phosphorylation and cell-cycle progression by a 20-residue peptide derived from p16CDKN2/INK4A, in Curr. Biol., vol. 6, n. 1, ENGLAND, Jan. 1996, pp. 84–91, DOI:10.1016/S0960-9822(02)00425-6, ISSN 0960-9822 (WC · ACNP), PMID 8805225.
^ M Serrano, , Beach D e David Beach, A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4, in Nature, vol. 366, n. 6456, ENGLAND, dicembre 1993, pp. 704–7, DOI:10.1038/366704a0, ISSN 0028-0836 (WC · ACNP), PMID 8259215.
^ K G Coleman, Morrissey D, Mulheron J, Sedman S A, Brinkley P, Price S, , Webster K R e KR Webster, Identification of CDK4 sequences involved in cyclin D1 and p16 binding, in J. Biol. Chem., vol. 272, n. 30, UNITED STATES, luglio 1997, pp. 18869–74, DOI:10.1074/jbc.272.30.18869, ISSN 0021-9258 (WC · ACNP), PMID 9228064.
^ A A Russo, Lee J O, Jeffrey P D, , Pavletich N P e Philip D. Jeffrey, Structural basis for inhibition of the cyclin-dependent kinase Cdk6 by the tumour suppressor p16INK4a, in Nature, vol. 395, n. 6699, ENGLAND, settembre 1998, pp. 237–43, DOI:10.1038/26155, ISSN 0028-0836 (WC · ACNP), PMID 9751050.
^ P Kaldis, Tong L, Mäkelä T P, , Solomon M J e MJ Solomon, CAK-independent Activation of CDK6 by a Viral Cyclin, in Mol. Biol. Cell, vol. 12, n. 12, United States, dicembre 2001, pp. 3987–99, ISSN 1059-1524 (WC · ACNP), PMC 60770, PMID 11739795.
^ Paula A Clark, , Peters Gordon e Gordon Peters, Multiple interacting domains contribute to p14ARF mediated inhibition of MDM2, in Oncogene, vol. 21, n. 29, England, luglio 2002, pp. 4498–507, DOI:10.1038/sj.onc.1205558, ISSN 0950-9232 (WC · ACNP), PMID 12085228.
^ J Pomerantz, Liégeois N J, Silverman A, Alland L, Chin L, Potes J, Chen K, Orlow I e Lee H W, The Ink4a tumor suppressor gene product, p19Arf, interacts with MDM2 and neutralizes MDM2's inhibition of p53, in Cell, vol. 92, n. 6, UNITED STATES, marzo 1998, pp. 713–23, DOI:10.1016/S0092-8674(00)81400-2, ISSN 0092-8674 (WC · ACNP), PMID 9529248.
^ M Vivo, Sansone F, Calabrò V, Parisi T, Borrelli L, Saviozzi S, , La Mantia G e G La Mantia, The human tumor suppressor arf interacts with spinophilin/neurabin II, a type 1 protein-phosphatase-binding protein, in J. Biol. Chem., vol. 276, n. 17, United States, aprile 2001, pp. 14161–9, DOI:10.1074/jbc.M006845200, ISSN 0021-9258 (WC · ACNP), PMID 11278317.

Voci correlate

Portale Biologia

Portale Chimica

[pmid15065884-1] Junan Li, , Tsai Ming-Daw, Muscarella Peter, Ming-Daw Tsai e Peter Muscarella, The nuclear protein p34SEI-1 regulates the kinase activity of cyclin-dependent kinase 4 in a concentration-dependent manner, in Biochemistry, vol. 43, n. 14, United States, aprile 2004, pp. 4394–9, DOI:10.1021/bi035601s, ISSN 0006-2960 (WC · ACNP), PMID 15065884.

[pmid10580009-2] M Sugimoto, Ohtani N, Hampson L, Hampson I N, Shimamoto A, Furuichi Y, Okumura K, Niwa S e Taya Y, Regulation of CDK4 activity by a novel CDK4-binding protein, p34SEI-1, in Genes Dev., vol. 13, n. 22, UNITED STATES, novembre 1999, pp. 3027–33, DOI:10.1101/gad.13.22.3027, ISSN 0890-9369 (WC · ACNP), PMC 317153, PMID 10580009.

[pmid12556559-3] Lili Zhao, Winckler Sarah, Korgaonkar Chandrashekhar, Tompkins Van, Horne Mary C, , Quelle Dawn E e DE Quelle, Cyclin G1 has growth inhibitory activity linked to the ARF-Mdm2-p53 and pRb tumor suppressor pathways, in Mol. Cancer Res., vol. 1, n. 3, United States, Jan. 2003, pp. 195–206, ISSN 1541-7786 (WC · ACNP), PMID 12556559.

[pmid18583933-4] Stacey M Ivanchuk, , Rutka James T e James T. Rutka, p14ARF interacts with DAXX: effects on HDM2 and p53, in Cell Cycle, vol. 7, n. 12, United States, giugno 2008, pp. 1836–50, DOI:10.4161/cc.7.12.6025, PMID 18583933.

[pmid14612427-5] Yanping Zhang, Bhat Krishna, Jin Aiwen, Allio Theresa, Burkhart William A, , Xiong Yue e Y. Xiong, Ribosomal Protein L11 Negatively Regulates Oncoprotein MDM2 and Mediates a p53-Dependent Ribosomal-Stress Checkpoint Pathway, in Mol. Cell. Biol., vol. 23, n. 23, United States, dicembre 2003, pp. 8902–12, DOI:10.1128/MCB.23.23.8902-8912.2003, ISSN 0270-7306 (WC · ACNP), PMC 262682, PMID 14612427.

[pmid12446718-6] Helen Rizos, Badhwar Prerna, Woodruff Sarah, Becker Therese M, Rooney Robert J, , Kefford Richard F e RF Kefford, Association of p14ARF with the p120E4F transcriptional repressor enhances cell cycle inhibition, in J. Biol. Chem., vol. 278, n. 7, United States, febbraio 2003, pp. 4981–9, DOI:10.1074/jbc.M210978200, ISSN 0021-9258 (WC · ACNP), PMID 12446718.

[pmid9529249-7] Y Zhang, , Yarbrough W G e Wendell G Yarbrough, ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways, in Cell, vol. 92, n. 6, UNITED STATES, marzo 1998, pp. 725–34, DOI:10.1016/S0092-8674(00)81401-4, ISSN 0092-8674 (WC · ACNP), PMID 9529249.

[pmid17353931-8] Rob M Ewing, Elisma Fred, Li Hongyan, Taylor Paul, Climie Shane, McBroom-Cerajewski Linda, Robinson Mark D, Connor Liam e Li Michael, Large-scale mapping of human protein–protein interactions by mass spectrometry, in Mol. Syst. Biol., vol. 3, n. 1, England, 2007, pp. 89, DOI:10.1038/msb4100134, PMC 1847948, PMID 17353931.

[pmid8805225-9] R Fåhraeus, Ball K L, Laín S, , Lane D P e David P. Lane, Inhibition of pRb phosphorylation and cell-cycle progression by a 20-residue peptide derived from p16CDKN2/INK4A, in Curr. Biol., vol. 6, n. 1, ENGLAND, Jan. 1996, pp. 84–91, DOI:10.1016/S0960-9822(02)00425-6, ISSN 0960-9822 (WC · ACNP), PMID 8805225.

[pmid8259215-10] M Serrano, , Beach D e David Beach, A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4, in Nature, vol. 366, n. 6456, ENGLAND, dicembre 1993, pp. 704–7, DOI:10.1038/366704a0, ISSN 0028-0836 (WC · ACNP), PMID 8259215.

[pmid9228064-11] K G Coleman, Morrissey D, Mulheron J, Sedman S A, Brinkley P, Price S, , Webster K R e KR Webster, Identification of CDK4 sequences involved in cyclin D1 and p16 binding, in J. Biol. Chem., vol. 272, n. 30, UNITED STATES, luglio 1997, pp. 18869–74, DOI:10.1074/jbc.272.30.18869, ISSN 0021-9258 (WC · ACNP), PMID 9228064.

[pmid9751050-12] A A Russo, Lee J O, Jeffrey P D, , Pavletich N P e Philip D. Jeffrey, Structural basis for inhibition of the cyclin-dependent kinase Cdk6 by the tumour suppressor p16INK4a, in Nature, vol. 395, n. 6699, ENGLAND, settembre 1998, pp. 237–43, DOI:10.1038/26155, ISSN 0028-0836 (WC · ACNP), PMID 9751050.

[pmid11739795-13] P Kaldis, Tong L, Mäkelä T P, , Solomon M J e MJ Solomon, CAK-independent Activation of CDK6 by a Viral Cyclin, in Mol. Biol. Cell, vol. 12, n. 12, United States, dicembre 2001, pp. 3987–99, ISSN 1059-1524 (WC · ACNP), PMC 60770, PMID 11739795.

[pmid12085228-14] Paula A Clark, , Peters Gordon e Gordon Peters, Multiple interacting domains contribute to p14ARF mediated inhibition of MDM2, in Oncogene, vol. 21, n. 29, England, luglio 2002, pp. 4498–507, DOI:10.1038/sj.onc.1205558, ISSN 0950-9232 (WC · ACNP), PMID 12085228.

[pmid9529248-15] J Pomerantz, Liégeois N J, Silverman A, Alland L, Chin L, Potes J, Chen K, Orlow I e Lee H W, The Ink4a tumor suppressor gene product, p19Arf, interacts with MDM2 and neutralizes MDM2's inhibition of p53, in Cell, vol. 92, n. 6, UNITED STATES, marzo 1998, pp. 713–23, DOI:10.1016/S0092-8674(00)81400-2, ISSN 0092-8674 (WC · ACNP), PMID 9529248.

[pmid11278317-16] M Vivo, Sansone F, Calabrò V, Parisi T, Borrelli L, Saviozzi S, , La Mantia G e G La Mantia, The human tumor suppressor arf interacts with spinophilin/neurabin II, a type 1 protein-phosphatase-binding protein, in J. Biol. Chem., vol. 276, n. 17, United States, aprile 2001, pp. 14161–9, DOI:10.1074/jbc.M006845200, ISSN 0021-9258 (WC · ACNP), PMID 11278317.

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