Ccnt1 12455

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Gene ID: 12455
Gene symbol: ccnt1
Gene Description: cyclin t1
Aliases: 2810478G24Rik; AI115585; CycT1
Human Ortholog Gene ID: [904]
Reviewer Judgement: TF Gene Candidate
Functional Classification: Transcription Factor Binding: tf co-factor binding
Homolog Cluster(s): 12455

Evidence:

Pubmed ID Function Species Evidence Strength Reviewer's Comments Reviewer
[12177005] Co-activation Human; Mouse Medium The (E.coli) synthesis and immobilization of Myc-GST fusions to glutatione-Sepharose beads with a HeLa nuclear extract wash demonstrate that (through Western blot analysis) cyclin T1 is able to bind a Myc-GST fusion. Cotransfection of a Myc deletion construct fusion to the Gal4 DNA binding domain in to murin NIH3T3 cells demonstrate that the Myc constructs (with region to bind cyclin T1) also retain the ability to activate the trifunctional enzyme carbamoyl-phosphate synthase/aspartate carbamoyltransferase/dihydroorotase (cad) promoter-luciferase reporter gene. Debra Fulton
[12588988] Co-activation Human; Other; Mouse Medium Yeast two-hybrid screen with a cyclin T1 construct as a bait against HeLa cDNA library linked to the GAL4 AD demonstrate a strong interaction (as determined by �-galactosidase activity levels) with partial cDNA sequence of growth factor granulin. C-terminal and N-terminal truncations of cyclin T1 expressed in E. coli and tested in the yeast two-hybrid system indicate that cyclin T1 interacts with granulin via its His-rich domain. Mouse NIH 3T3 cells elicit only a weak response to Tat and coexpression of human cyclin T1 in mouse NIH3T3 cells allows a robust transactivation which is repressed by the granulin/epithelin precursor (GEP) (assaying the expression of luciferase under the control of the HIV-1 long terminal repeat). Debra Fulton
[9499409] Other Other Medium CDK9 forms complexes with cyclin T1 or T2 Jared Roach
[12588988] Other Mouse Weak Seems to have a direct physcial role in transcription of HIV virus.

"Cyclin T1, together with the kinase CDK9, is a component of the transcription elongation factor P-TEFb ...... P-TEFb facilitates transcription by phosphorylating the carboxy-terminal domain (CTD) of RNA polymerase II..... Granulin expression inhibited Tat transactivation, and tethering experiments showed that this effect was due, at least in part, to a direct action on cyclin T1 in the absence of Tat. Thus, granulin is a cellular protein that interacts with cyclin T1 to inhibit transcription."

Jared Roach
Additional Reviewer Comments:
Reviewer: Jared Roach

OMIM: "Peng et al. (1998) demonstrated that CDK9 forms complexes with either cyclin T1 or cyclin T2 (603862) in HeLa cell nuclear extracts. Approximately 80% of CDK9 is complexed with cyclin T1. Each CDK9/cyclin T complex is an active positive transcription elongation factor b (P-TEFb; see also 603251) molecule that can phosphorylate the C-terminal domain of the largest subunit of RNA polymerase II (POLR2A; 180660) and facilitate the transition from abortive elongation into productive elongation" So it would seem that Ccnt1 should not be considered a TF. However, if may be a TF co-factor for HIV, as OMIM also has: "Wei et al. (1998) isolated an 87-kD cyclin C-related protein, designated cyclin T, which interacts specifically with the transactivation domain of Tat." But considering the evidence that the main function of this protein is not that of a TF, and that we are primarily focusing on mouse TFs (not HIV TFs), during my initial curation, I considered Ccnt1 to not be a TF. However, Debra has curated it as a "TF Gene Candidate", and I agree that ths is a reasonable interpretation of the available data and of our ontology, so I have updated my classification to "TF Gene Candidate".

Reviewer: Debra Fulton

Cyclin T1 is a component of P-TEFb and acts as a co-factor in transcription elongation. P-TEFb facilitates transcription by phosphorylating the carboxy-terminal domain (CTD) of RNA polymerase II. Recruitment of cyclin T1 to the cad promoter via a Gal4 fusion protein or through protein-protein interaction with the HIV-1 Tat protein activates cad transcription. Binding of granulin to cyclin T1 inhibits the phosphorylation of a CTD peptide and inhibits Tat transactivation.


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Facts about Ccnt1 12455RDF feed
Gene description cyclin t1  +
Gene id 12,455  +
Gene judgment TF Gene Candidate  +
Gene symbol ccnt1  +, 2810478G24Rik  +, AI115585  +, and CycT1  +
Gene taxonomy Transcription Factor Binding: tf co-factor binding  +
Homolog cluster 12,455  +
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