1bi7: Difference between revisions

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~~[[Image:1bi7.png|left|200px]]~~

===MECHANISM OF G1 CYCLIN DEPENDENT KINASE INHIBITION FROM THE STRUCTURE OF THE CDK6-P16INK4A TUMOR SUPPRESSOR COMPLEX===

==~~=MECHANISM OF G1 CYCLIN DEPENDENT KINASE INHIBITION FROM THE STRUCTURE OF THE CDK6-P16INK4A TUMOR SUPPRESSOR COMPLEX~~===

==Disease==

[[http://www.uniprot.org/uniprot/CD2A1_HUMAN CD2A1_HUMAN]] Note=The association between cutaneous and uveal melanomas in some families suggests that mutations in CDKN2A may account for a proportion of uveal melanomas. However, CDKN2A mutations are rarely found in uveal melanoma patients. Defects in CDKN2A are the cause of cutaneous malignant melanoma type 2 (CMM2) [MIM:[http://omim.org/entry/155601 155601]]. Malignant melanoma is a malignant neoplasm of melanocytes, arising de novo or from a pre-existing benign nevus, which occurs most often in the skin but also may involve other sites.<ref>PMID:7987387</ref><ref>PMID:8595405</ref><ref>PMID:8653684</ref><ref>PMID:8710906</ref><ref>PMID:9328469</ref><ref>PMID:9425228</ref><ref>PMID:10651484</ref><ref>PMID:11506491</ref><ref>PMID:12019208</ref><ref>PMID:10874641</ref><ref>PMID:14646619</ref><ref>PMID:19260062</ref> Defects in CDKN2A are the cause of familial atypical multiple mole melanoma-pancreatic carcinoma syndrome (FAMMMPC) [MIM:[http://omim.org/entry/606719 606719]]. Defects in CDKN2A are a cause of Li-Fraumeni syndrome (LFS) [MIM:[http://omim.org/entry/151623 151623]]. LFS is a highly penetrant familial cancer phenotype usually associated with inherited mutations in TP53.<ref>PMID:10484981</ref> Defects in CDKN2A are the cause of melanoma-astrocytoma syndrome (MASTS) [MIM:[http://omim.org/entry/155755 155755]]. The melanoma-astrocytoma syndrome is characterized by a dual predisposition to melanoma and neural system tumors, commonly astrocytoma.<ref>PMID:11136714</ref>

~~{{ABSTRACT_PUBMED_9751050}}~~

==Function==

[[http://www.uniprot.org/uniprot/CDK6_HUMAN CDK6_HUMAN]] Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition. Phosphorylates pRB/RB1 and NPM1. Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle. Involved in initiation and maintenance of cell cycle exit during cell differentiation; prevents cell proliferation and regulates negatively cell differentiation, but is required for the proliferation of specific cell types (e.g. erythroid and hematopoietic cells). Essential for cell proliferation within the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. Required during thymocyte development. Promotes the production of newborn neurons, probably by modulating G1 length. Promotes, at least in astrocytes, changes in patterns of gene expression, changes in the actin cytoskeleton including loss of stress fibers, and enhanced motility during cell differentiation. Prevents myeloid differentiation by interfering with RUNX1 and reducing its transcription transactivation activity, but promotes proliferation of normal myeloid progenitors. Delays senescence. Promotes the proliferation of beta-cells in pancreatic islets of Langerhans.<ref>PMID:8114739</ref><ref>PMID:12833137</ref><ref>PMID:14985467</ref><ref>PMID:15254224</ref><ref>PMID:15809340</ref><ref>PMID:17431401</ref><ref>PMID:17420273</ref><ref>PMID:20668294</ref><ref>PMID:20333249</ref> [[http://www.uniprot.org/uniprot/CD2A1_HUMAN CD2A1_HUMAN]] Acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6. This inhibits their ability to interact with cyclins D and to phosphorylate the retinoblastoma protein.<ref>PMID:7972006</ref><ref>PMID:16782892</ref>

==About this Structure==

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==Reference==

[[Category: Homo sapiens]]

[[Category: Jeffrey, P D.]]

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@@ Line 1: / Line 1: @@
-[[Image:1bi7.png|left|200px]]
 {{STRUCTURE_1bi7|  PDB=1bi7  |  SCENE=  }}
+===MECHANISM OF G1 CYCLIN DEPENDENT KINASE INHIBITION FROM THE STRUCTURE OF THE CDK6-P16INK4A TUMOR SUPPRESSOR COMPLEX===
+{{ABSTRACT_PUBMED_9751050}}
-===MECHANISM OF G1 CYCLIN DEPENDENT KINASE INHIBITION FROM THE STRUCTURE OF THE CDK6-P16INK4A TUMOR SUPPRESSOR COMPLEX===
+==Disease==
+[[http://www.uniprot.org/uniprot/CD2A1_HUMAN CD2A1_HUMAN]] Note=The association between cutaneous and uveal melanomas in some families suggests that mutations in CDKN2A may account for a proportion of uveal melanomas. However, CDKN2A mutations are rarely found in uveal melanoma patients.  Defects in CDKN2A are the cause of cutaneous malignant melanoma type 2 (CMM2) [MIM:[http://omim.org/entry/155601 155601]]. Malignant melanoma is a malignant neoplasm of melanocytes, arising de novo or from a pre-existing benign nevus, which occurs most often in the skin but also may involve other sites.<ref>PMID:7987387</ref><ref>PMID:8595405</ref><ref>PMID:8653684</ref><ref>PMID:8710906</ref><ref>PMID:9328469</ref><ref>PMID:9425228</ref><ref>PMID:10651484</ref><ref>PMID:11506491</ref><ref>PMID:12019208</ref><ref>PMID:10874641</ref><ref>PMID:14646619</ref><ref>PMID:19260062</ref>  Defects in CDKN2A are the cause of familial atypical multiple mole melanoma-pancreatic carcinoma syndrome (FAMMMPC) [MIM:[http://omim.org/entry/606719 606719]].  Defects in CDKN2A are a cause of Li-Fraumeni syndrome (LFS) [MIM:[http://omim.org/entry/151623 151623]]. LFS is a highly penetrant familial cancer phenotype usually associated with inherited mutations in TP53.<ref>PMID:10484981</ref>  Defects in CDKN2A are the cause of melanoma-astrocytoma syndrome (MASTS) [MIM:[http://omim.org/entry/155755 155755]]. The melanoma-astrocytoma syndrome is characterized by a dual predisposition to melanoma and neural system tumors, commonly astrocytoma.<ref>PMID:11136714</ref>
-{{ABSTRACT_PUBMED_9751050}}
+==Function==
+[[http://www.uniprot.org/uniprot/CDK6_HUMAN CDK6_HUMAN]] Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition. Phosphorylates pRB/RB1 and NPM1. Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle. Involved in initiation and maintenance of cell cycle exit during cell differentiation; prevents cell proliferation and regulates negatively cell differentiation, but is required for the proliferation of specific cell types (e.g. erythroid and hematopoietic cells). Essential for cell proliferation within the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. Required during thymocyte development. Promotes the production of newborn neurons, probably by modulating G1 length. Promotes, at least in astrocytes, changes in patterns of gene expression, changes in the actin cytoskeleton including loss of stress fibers, and enhanced motility during cell differentiation. Prevents myeloid differentiation by interfering with RUNX1 and reducing its transcription transactivation activity, but promotes proliferation of normal myeloid progenitors. Delays senescence. Promotes the proliferation of beta-cells in pancreatic islets of Langerhans.<ref>PMID:8114739</ref><ref>PMID:12833137</ref><ref>PMID:14985467</ref><ref>PMID:15254224</ref><ref>PMID:15809340</ref><ref>PMID:17431401</ref><ref>PMID:17420273</ref><ref>PMID:20668294</ref><ref>PMID:20333249</ref> [[http://www.uniprot.org/uniprot/CD2A1_HUMAN CD2A1_HUMAN]] Acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6. This inhibits their ability to interact with cyclins D and to phosphorylate the retinoblastoma protein.<ref>PMID:7972006</ref><ref>PMID:16782892</ref>
 ==About this Structure==
@@ Line 14: / Line 16: @@
 ==Reference==
-<ref group="xtra">PMID:009751050</ref><references group="xtra"/>
+<ref group="xtra">PMID:009751050</ref><references group="xtra"/><references/>
 [[Category: Homo sapiens]]
 [[Category: Jeffrey, P D.]]