Ver el código de «Cdk4»

{{Ficha de proteína
 | Name = Cyclin-dependent kinase 4
 | image = Protein_CDK4_PDB_1LD2.png
 | image_source = Rendering based on [[Protein_Data_Bank | PDB]] {{PDB2|1LD2}}.
 | PDB = {{PDB2|1LD2}}, {{PDB2|2W96}}, {{PDB2|2W99}}, {{PDB2|2W9F}}, {{PDB2|2W9Z}}, {{PDB2|3G33}}
 | HGNCid = 1773
 | MGIid = 88357
 | Symbol = CDK4
 | AltSymbols =; CMM3; PSK-J3
 | IUPHAR = 
 | ChEMBL = 331
 | OMIM = 123829
 | ECnumber = 2.7.11.22
 | Homologene = 55429
 | GeneAtlas_image1 = PBB_GE_CDK4_202246_s_at_tn.png
 | GeneAtlas_image2 = 
 | GeneAtlas_image3 = 
 | Protein_domain_image = 
 | Function = {{GNF_GO|id=GO:0004693 |text = cyclin-dependent protein serine/threonine kinase activity}} {{GNF_GO|id=GO:0005515 |text = protein binding}} {{GNF_GO|id=GO:0005524 |text = ATP binding}} {{GNF_GO|id=GO:0016538 |text = cyclin-dependent protein serine/threonine kinase regulator activity}} {{GNF_GO|id=GO:0030332 |text = cyclin binding}} {{GNF_GO|id=GO:0032403 |text = protein complex binding}}
 | Component = {{GNF_GO|id=GO:0000307 |text = cyclin-dependent protein kinase holoenzyme complex}} {{GNF_GO|id=GO:0000785 |text = chromatin}} {{GNF_GO|id=GO:0005634 |text = nucleus}} {{GNF_GO|id=GO:0005654 |text = nucleoplasm}} {{GNF_GO|id=GO:0005667 |text = transcription factor complex}} {{GNF_GO|id=GO:0005730 |text = nucleolus}} {{GNF_GO|id=GO:0005829 |text = cytosol}} {{GNF_GO|id=GO:0005923 |text = bicellular tight junction}} {{GNF_GO|id=GO:0031965 |text = nuclear membrane}} {{GNF_GO|id=GO:0048471 |text = perinuclear region of cytoplasm}}
 | Process = {{GNF_GO|id=GO:0000082 |text = G1/S transition of mitotic cell cycle}} {{GNF_GO|id=GO:0000278 |text = mitotic cell cycle}} {{GNF_GO|id=GO:0002088 |text = lens development in camera-type eye}} {{GNF_GO|id=GO:0006325 |text = chromatin organization}} {{GNF_GO|id=GO:0006468 |text = protein phosphorylation}} {{GNF_GO|id=GO:0007165 |text = signal transduction}} {{GNF_GO|id=GO:0007623 |text = circadian rhythm}} {{GNF_GO|id=GO:0008284 |text = positive regulation of cell proliferation}} {{GNF_GO|id=GO:0009636 |text = response to toxic substance}} {{GNF_GO|id=GO:0010288 |text = response to lead ion}} {{GNF_GO|id=GO:0010468 |text = regulation of gene expression}} {{GNF_GO|id=GO:0010971 |text = positive regulation of G2/M transition of mitotic cell cycle}} {{GNF_GO|id=GO:0031100 |text = organ regeneration}} {{GNF_GO|id=GO:0033574 |text = response to testosterone}} {{GNF_GO|id=GO:0042493 |text = response to drug}} {{GNF_GO|id=GO:0043065 |text = positive regulation of apoptotic process}} {{GNF_GO|id=GO:0045727 |text = positive regulation of translation}} {{GNF_GO|id=GO:0045793 |text = positive regulation of cell size}} {{GNF_GO|id=GO:0045859 |text = regulation of protein kinase activity}} {{GNF_GO|id=GO:0048146 |text = positive regulation of fibroblast proliferation}} {{GNF_GO|id=GO:0051301 |text = cell division}} {{GNF_GO|id=GO:0055093 |text = response to hyperoxia}} {{GNF_GO|id=GO:0071157 |text = negative regulation of cell cycle arrest}}
 | Hs_EntrezGene = 1019
 | Hs_Ensembl = ENSG00000135446
 | Hs_RefseqmRNA = NM_000075
 | Hs_RefseqProtein = NP_000066
 | Hs_GenLoc_db = hg38
 | Hs_GenLoc_chr = 12
 | Hs_GenLoc_start = 57747727
 | Hs_GenLoc_end = 57756013
 | Hs_Uniprot = P11802
 | Mm_EntrezGene = 12567
 | Mm_Ensembl = ENSMUSG00000006728
 | Mm_RefseqmRNA = NM_009870
 | Mm_RefseqProtein = NP_034000
 | Mm_GenLoc_db = mm10
 | Mm_GenLoc_chr = 10
 | Mm_GenLoc_start = 127063534
 | Mm_GenLoc_end = 127067920
 | Mm_Uniprot = P30285
 | path = PBB/1019
}}
La '''quinasa dependiente de ciclina 4''' también conocida como '''Cdk4''', es una [[enzima]] que en los humanos es codificado por el gen ''CDK4''. Como su nombre lo indica, la Cdk4 es miembro de la familia de [[Quinasa dependiente de ciclina|quinasas dependientes de ciclinas]] y miembro de la familia de las [[Serina/treonina proteína kinasa|serina/treonina proteína kinasas]], que presenta un alto grado de [[homología (biología)|homología]] con [[Cdc28]] sintetizada por la especie ''[[Saccharomyces cerevisiae|S. cerevisiae]]'' y [[cdc2]] de la especie ''[[Schizosaccharomyces pombe|S. pombe]]''.

== Función ==
La serina/treonina proteína quinasa del Cdk4 es una subunidad catalítica importante para la progresión de la célula por la [[fase G]] del [[ciclo celular]]. La actividad de esta quinasa está restringida a la [[fase G1]]-[[fase S|S]], y controlada o modulada por las subunidades regulatorias de la [[Ciclina D|ciclina tipo D]] y del inhibitor de las Cdk, [[p16|p16<sup>INK4a</sup>]]. Esta quinasa ha sido responsable de la [[fosforilación]] de la [[proteína del retinoblastoma]] (pRb).<ref name="entrez">{{Cita web|title = Entrez Gene: CDK4 cyclin-dependent kinase 4|url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1019|accessdate = }}</ref>

== Importancia clínica ==
Mutaciones en Cdk4, así como en su proteínas asociadas, incluyendo las ciclinas D, p16 (TINTA4un) y pRb se encuentran en cercana asociación con la [[carcinogénesis]] en una variedad de órganos. En este respecto se han descubierto múltiples secuencias del gen ''CDK4'' que son sitios poliadenilación, un proceso que es parte de la expresión genética del gen.<ref name="entrez">{{Cita web|title = Entrez Gene: CDK4 cyclin-dependent kinase 4|url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1019|accessdate = }}</ref>

El medicamento [[Palbociclib]], aprobado por la [[Administración de Alimentos y Medicamentos]] estadounidense para tratar el [[cáncer de seno]] en estadio avanzado (metastásico), tiene una fuerte asociación con Cdk4 y [[CDK6]].<ref>{{Cite journal | pmid = 19874578 | year = 2009 | last1 = Finn | first1 = RS | last2 = Dering | first2 = J | last3 = Conklin | first3 = D | last4 = Kalous | first4 = O | last5 = Cohen | first5 = DJ | last6 = Desai | first6 = AJ | last7 = Ginther | first7 = C | last8 = Atefi | first8 = M | last9 = Chen | first9 = I | last10 = Fowst | first10 = Camilla | last11 = Los | first11 = Gerret | last12 = Slamon | first12 = Dennis J | title = PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro | volume = 11 | issue = 5 | pages = R77 | doi = 10.1186/bcr2419 | pmc = 2790859 | journal = Breast cancer research : BCR| display-authors = 8 }}</ref><ref name="pmid24369047">{{cite journal | author = Rocca A, Farolfi A, Bravaccini S, Schirone A, Amadori D | title = Palbociclib (PD 0332991): targeting the cell cycle machinery in breast cancer | journal = Expert Opin Pharmacother | volume = 15 | issue = 3 | pages = 407–20 | year = 2014 | pmid = 24369047 | doi = 10.1517/14656566.2014.870555 }}</ref>

== Interacciones ==
[[Archivo:Signal_transduction_pathways.svg|left|thumb|300x300px|Visión general de la vía de transducción de señales asociada con la [[apoptosis]]. Cdk4 está en el núcleo, del lado derecho de la imagen.]]

La quinasa dependiente de ciclina 4 ha demostrado ser capaz de [[Interacciones proteína-proteína|interaccionar]] con:

* [[CDC37]],<ref name = pmid17353931>{{cite journal | author = Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D | title = Large-scale mapping of human protein-protein interactions by mass spectrometry | journal = Mol. Syst. Biol. | volume = 3 | issue = 1| pages = 89 | year = 2007 | pmid = 17353931 | pmc = 1847948 | doi = 10.1038/msb4100134}}</ref><ref name = pmid8703009>{{cite journal | author = Dai K, Kobayashi R, Beach D | title = Physical interaction of mammalian CDC37 with CDK4 | journal = J. Biol. Chem. | volume = 271 | issue = 36 | pages = 22030–4 | year = 1996 | pmid = 8703009 | doi = 10.1074/jbc.271.36.22030}}</ref><ref name = pmid9150368>{{cite journal | author = Lamphere L, Fiore F, Xu X, Brizuela L, Keezer S, Sardet C, Draetta GF, Gyuris J | title = Interaction between Cdc37 and Cdk4 in human cells | journal = Oncogene | volume = 14 | issue = 16 | pages = 1999–2004 | year = 1997 | pmid = 9150368 | doi = 10.1038/sj.onc.1201036}}</ref><ref name = pmid8666233>{{cite journal | author = Stepanova L, Leng X, Parker SB, Harper JW | title = Mammalian p50Cdc37 is a protein kinase-targeting subunit of Hsp90 that binds and stabilizes Cdk4 | journal = Genes Dev. | volume = 10 | issue = 12 | pages = 1491–502 | year = 1996 | pmid = 8666233 | doi = 10.1101/gad.10.12.1491}}</ref> 
* [[CDKN1B]],<ref name = pmid11360184/><ref name = pmid10908655/>
* [[CDKN2B]],<ref name = pmid16189514/><ref name = pmid16169070>{{cite journal | pmid = | author = Ghavidel A, Cagney G, Emili A | title = A skeleton of the human protein interactome | journal = Cell | volume = 122 | issue = 6 | pages = 830–2 | year = 2005 | doi = 10.1016/j.cell.2005.09.006}}</ref> 
* [[CDKN2C]],<ref name = pmid17353931/><ref name = pmid8001816>{{cite journal | author = Guan KL, Jenkins CW, Li Y, Nichols MA, Wu X, O'Keefe CL, Matera AG, Xiong Y | title = Growth suppression by p18, a p16INK4/MTS1- and p14INK4B/MTS2-related CDK6 inhibitor, correlates with wild-type pRb function | journal = Genes Dev. | volume = 8 | issue = 24 | pages = 2939–52 | year = 1994 | pmid = 8001816 | doi = 10.1101/gad.8.24.2939}}</ref> 
* [[CEBPA]],<ref name = pmid11684017>{{cite journal | author = Wang H, Iakova P, Wilde M, Welm A, Goode T, Roesler WJ, Timchenko NA | title = C/EBPalpha arrests cell proliferation through direct inhibition of Cdk2 and Cdk4 | journal = Mol. Cell | volume = 8 | issue = 4 | pages = 817–28 | year = 2001 | pmid = 11684017 | doi = 10.1016/S1097-2765(01)00366-5}}</ref> 
* [[Cyclin D1|CCND1]],<ref name = pmid10580009/><ref name = pmid8259215/><ref name = pmid11360184/><ref name = pmid9837900>{{cite journal | author = Taulés M, Rius E, Talaya D, López-Girona A, Bachs O, Agell N | title = Calmodulin is essential for cyclin-dependent kinase 4 (Cdk4) activity and nuclear accumulation of cyclin D1-Cdk4 during G1 | journal = J. Biol. Chem. | volume = 273 | issue = 50 | pages = 33279–86 | year = 1998 | pmid = 9837900 | doi = 10.1074/jbc.273.50.33279}}</ref><ref name = pmid10908655>{{cite journal | author = Cariou S, Donovan JC, Flanagan WM, Milic A, Bhattacharya N, Slingerland JM | title = Down-regulation of p21WAF1/CIP1 or p27Kip1 abrogates antiestrogen-mediated cell cycle arrest in human breast cancer cells | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 97 | issue = 16 | pages = 9042–6 | year = 2000 | pmid = 10908655 | pmc = 16818 | doi = 10.1073/pnas.160016897}}</ref><ref name = pmid9228064>{{cite journal | author = Coleman KG, Wautlet BS, Morrissey D, Mulheron J, Sedman SA, Brinkley P, Price S, Webster KR | title = Identification of CDK4 sequences involved in cyclin D1 and p16 binding | journal = J. Biol. Chem. | volume = 272 | issue = 30 | pages = 18869–74 | year = 1997 | pmid = 9228064 | doi = 10.1074/jbc.272.30.18869}}</ref> 
* [[Cyclin D3|CCND3]],<ref name = pmid16189514>{{cite journal | author = Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M | title = Towards a proteome-scale map of the human protein-protein interaction network | journal = Nature | volume = 437 | issue = 7062 | pages = 1173–8 | year = 2005 | pmid = 16189514 | doi = 10.1038/nature04209}}</ref><ref name = pmid14641107>{{cite journal | author = Arsenijevic T, Degraef C, Dumont JE, Roger PP, Pirson I | title = A novel partner for D-type cyclins: protein kinase A-anchoring protein AKAP95 | journal = Biochem. J. | volume = 378 | issue = Pt 2 | pages = 673–9 | year = 2004 | pmid = 14641107 | pmc = 1223988 | doi = 10.1042/BJ20031765}}</ref><ref name = pmid11360184>{{cite journal | author = Lin J, Jinno S, Okayama H | title = Cdk6-cyclin D3 complex evades inhibition by inhibitor proteins and uniquely controls cell's proliferation competence | journal = Oncogene | volume = 20 | issue = 16 | pages = 2000–9 | year = 2001 | pmid = 11360184 | doi = 10.1038/sj.onc.1204375}}</ref><ref name = pmid10342870>{{cite journal | author = Zhang Q, Wang X, Wolgemuth DJ | title = Developmentally regulated expression of cyclin D3 and its potential in vivo interacting proteins during murine gametogenesis | journal = Endocrinology | volume = 140 | issue = 6 | pages = 2790–800 | year = 1999 | pmid = 10342870 | doi = 10.1210/endo.140.6.6756}}</ref> 
* [[Drebrin-like|DBNL]],<ref name = pmid17353931/> 
* [[MyoD]],<ref name = pmid10601020>{{cite journal | author = Zhang JM, Zhao X, Wei Q, Paterson BM | title = Direct inhibition of G(1) cdk kinase activity by MyoD promotes myoblast cell cycle withdrawal and terminal differentiation | journal = EMBO J. | volume = 18 | issue = 24 | pages = 6983–93 | year = 1999 | pmid = 10601020 | pmc = 1171761 | doi = 10.1093/emboj/18.24.6983}}</ref><ref name = pmid10022835>{{cite journal | author = Zhang JM, Wei Q, Zhao X, Paterson BM | title = Coupling of the cell cycle and myogenesis through the cyclin D1-dependent interaction of MyoD with cdk4 | journal = EMBO J. | volume = 18 | issue = 4 | pages = 926–33 | year = 1999 | pmid = 10022835 | pmc = 1171185 | doi = 10.1093/emboj/18.4.926}}</ref> 
* [[P16 (gene) | P16]],<ref name = pmid17353931/><ref name = pmid8805225>{{cite journal | author = Fåhraeus R, Paramio JM, Ball KL, Laín S, Lane DP | title = Inhibition of pRb phosphorylation and cell-cycle progression by a 20-residue peptide derived from p16CDKN2/INK4A | journal = Curr. Biol. | volume = 6 | issue = 1 | pages = 84–91 | year = 1996 | pmid = 8805225 | doi = 10.1016/S0960-9822(02)00425-6}}</ref><ref name = pmid15065884/><ref name = pmid10580009/><ref name = pmid8259215/><ref name = pmid9228064/> 
* [[PCNA]],<ref name = pmid8259215>{{cite journal | pmid = | author = Nasmyth K, Hunt T | title = Cell cycle. Dams and sluices | journal = Nature | volume = 366 | issue = 6456 | pages = 634–5 | year = 1993 | doi = 10.1038/366634a0}}</ref><ref name = pmid8101826>{{cite journal | author = Xiong Y, Zhang H, Beach D | title = Subunit rearrangement of the cyclin-dependent kinases is associated with cellular transformation | journal = Genes Dev. | volume = 7 | issue = 8 | pages = 1572–83 | year = 1993 | pmid = 8101826 | doi = 10.1101/gad.7.8.1572}}</ref>  and
* [[SERTAD1]].<ref name = pmid15065884>{{cite journal | author = Li J, Melvin WS, Tsai MD, Muscarella P | title = The nuclear protein p34SEI-1 regulates the kinase activity of cyclin-dependent kinase 4 in a concentration-dependent manner | journal = Biochemistry | volume = 43 | issue = 14 | pages = 4394–9 | year = 2004 | pmid = 15065884 | doi = 10.1021/bi035601s}}</ref><ref name = pmid10580009>{{cite journal | author = Sugimoto M, Nakamura T, Ohtani N, Hampson L, Hampson IN, Shimamoto A, Furuichi Y, Okumura K, Niwa S, Taya Y, Hara E | title = Regulation of CDK4 activity by a novel CDK4-binding protein, p34(SEI-1) | journal = Genes Dev. | volume = 13 | issue = 22 | pages = 3027–33 | year = 1999 | pmid = 10580009 | pmc = 317153 | doi = 10.1101/gad.13.22.3027}}</ref>

== Referencias ==
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{{Control de autoridades}}
[[Categoría:Ciclo celular]]
[[Categoría:Proteínas humanas]]
[[Categoría:Proteínas]]