CCR4-Not
{{short description|Multiprotein complex used in gene expression}}
File:PDB-4C0D-CNOT1-2-3-TC.png
Carbon Catabolite Repression 4—Negative On TATA-less, or CCR4-Not, is a multiprotein complex that functions in gene expression.{{cite journal | last=Collart | first=Martine A. | title=The Ccr4-Not complex is a key regulator of eukaryotic gene expression | journal=Wiley Interdisciplinary Reviews: RNA | publisher=Wiley | volume=7 | issue=4 | date=2016-01-29 | issn=1757-7004 | doi=10.1002/wrna.1332 | pages=438–454| pmid=26821858 | pmc=5066686 }}{{cite journal | last1=Miller | first1=Jason E. | last2=Reese | first2=Joseph C. | title=Ccr4-Not complex: the control freak of eukaryotic cells | journal=Critical Reviews in Biochemistry and Molecular Biology | publisher=Informa UK Limited | volume=47 | issue=4 | date=2012-03-15 | issn=1040-9238 | doi=10.3109/10409238.2012.667214 | pages=315–333| pmid=22416820 | pmc=3376659 }} The complex has multiple enzymatic activities as both a poly(A) 3′-5′ exonuclease and a ubiquitin ligase.{{cite journal | last1=Aslam | first1=Akhmed | last2=Mittal | first2=Saloni | last3=Koch | first3=Frederic | last4=Andrau | first4=Jean-Christophe | last5=Winkler | first5=G. Sebastiaan | editor-last=Wickens | editor-first=Marvin | title=The Ccr4–Not Deadenylase Subunits CNOT7 and CNOT8 Have Overlapping Roles and Modulate Cell Proliferation | journal=Molecular Biology of the Cell | publisher=American Society for Cell Biology (ASCB) | volume=20 | issue=17 | year=2009 | issn=1059-1524 | doi=10.1091/mbc.e09-02-0146 | pages=3840–3850| pmid=19605561 | pmc=2735483 }}{{cite journal | vauthors = Chen J, Chiang YC, Denis CL | title = CCR4, a 3′-5′ poly(A) RNA and ssDNA exonuclease, is the catalytic component of the cytoplasmic deadenylase | journal = EMBO J | volume = 21 | issue = 6 | pages = 1414–26 |date=Mar 2002 | pmid = 11889047 | pmc = 125924 | doi = 10.1093/emboj/21.6.1414 }}{{cite web | title = Entrez Gene: CNOT6 CCR4-NOT transcription complex, subunit 6| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=57472| accessdate = }}{{cite journal | last1=Albert | first1=Thomas K. | last2=Hanzawa | first2=Hiroyuki | last3=Legtenberg | first3=Yvonne I.A. | last4=de Ruwe | first4=Marjolein J. | last5=van den Heuvel | first5=Fiona A.J. | last6=Collart | first6=Martine A. | last7=Boelens | first7=Rolf | last8=Timmers | first8=H.Th.Marc | title=Identification of a ubiquitin-protein ligase subunit within the CCR4-NOT transcription repressor complex | journal=The EMBO Journal | publisher=Wiley | volume=21 | issue=3 | date=2002-02-01 | issn=0261-4189 | doi=10.1093/emboj/21.3.355 | pages=355–364| pmid=11823428 | pmc=125831 }} The exonuclease activity of CCR4-Not shortens the poly(A) tail found at 3' end of almost every eukaryotic mRNA.{{Cite journal |last1=Stowell |first1=James A. W. |last2=Webster |first2=Michael W. |last3=Kögel |first3=Alexander |last4=Wolf |first4=Jana |last5=Shelley |first5=Kathryn L. |last6=Passmore |first6=Lori A. |date=2016-11-15 |title=Reconstitution of Targeted Deadenylation by the Ccr4-Not Complex and the YTH Domain Protein Mmi1 |journal=Cell Reports |volume=17 |issue=8 |pages=1978–1989 |doi=10.1016/j.celrep.2016.10.066 |issn=2211-1247 |pmc=5120349 |pmid=27851962}} The complex is present both in the nucleus where it regulates transcription and in the cytoplasm where it associates with translating ribosomes and RNA processing bodies. In mammalian cell, it has a function in the regulation of the cell cycle, chromatin modification, activation and inhibition of transcription initiation, control of transcription elongation, RNA export, nuclear RNA surveillance, and DNA damage repair in nucleus. Ccr4–Not complex plays an important role in mRNA decay and protein quality control in the cytoplasm.{{Cite journal |last1=Chalabi Hagkarim |first1=Nafiseh |last2=Grand |first2=Roger J. |date=2020-10-29 |title=The Regulatory Properties of the Ccr4–Not Complex |journal=Cells |volume=9 |issue=11 |pages=2379 |doi=10.3390/cells9112379 |issn=2073-4409 |pmc=7692201 |pmid=33138308 |doi-access=free}}
Subunits
The human CCR4-Not complex is composed of structural (non-catalytic) subunits and those that have exonuclease and E3 ligase activity. Some but not all of the human subunits are conserved in budding yeast.{{cite journal | last=Albert | first=T. K. | title=Isolation and characterization of human orthologs of yeast CCR4-NOT complex subunits | journal=Nucleic Acids Research | publisher=Oxford University Press (OUP) | volume=28 | issue=3 | date=2000-02-01 | issn=1362-4962 | doi=10.1093/nar/28.3.809 | pages=809–817| pmid=10637334 | pmc=102560 | doi-access=free }} In yeast the complex has nine core subunits, comprising Ccr4 (carbon catabolite repression), Caf proteins (Ccr4 associated factor) (Caf1, Caf40, Caf130) and Not proteins (Not1, Not2, Not3, Not4, and Not5).{{Cite journal |last=Collart |first=Martine A |date=2003-08-14 |title=Global control of gene expression in yeast by the Ccr4-Not complex |url=https://www.sciencedirect.com/science/article/pii/S0378111903006723 |journal=Gene |volume=313 |pages=1–16 |doi=10.1016/S0378-1119(03)00672-3 |pmid=12957374 |issn=0378-1119|url-access=subscription }}
{{note label|rounding|A|A}}Molecular weight of human subunits from Uniprot.
See also
References
{{Reflist}}
{{MolBioGeneExp}}