Key component of the super elongation complex (SEC), a complex required to increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by the polymerase at multiple sites along the DNA. In the SEC complex, AFF4 acts as a central scaffold that recruits other factors through direct interactions with ELL proteins (ELL, ELL2 or ELL3) and the P-TEFb complex. In case of infection by HIV-1 virus, the SEC complex is recruited by the viral Tat protein to stimulate viral gene expression.
|Gene References into Functions
- The TAR central loop contacts the CycT1 Tat-TAR recognition motif (TRM) and the second Tat Zn(2+)-binding loop. Hydrogen-deuterium exchange (HDX) shows that AFF4 helix 2 is stabilized in the TAR complex despite not touching the RNA, explaining how it enhances TAR binding to the SEC 50-fold. PMID: 27731797
- AFF4 is positioned to make unexpected direct contacts with HIV Tat, and Tat enhances P-TEFb/CCNT1 affinity for AFF4. PMID: 23471103
- missense mutations in AFF4 in three unrelated probands with a new syndrome that phenotypically overlaps Cornelia de Lange syndrome (CdLS) that was named CHOPS syndrome (C for cognitive impairment and coarse facies, H for heart defects, O for obesity, P for pulmonary involvement and S for short stature and skeletal dysplasia) PMID: 25730767
- HIV-1 Tat recruits transcription elongation factors dispersed along a flexible AFF4 scaffold. PMID: 23251033
- overexpression of AFF2/3/4 interferes with the organization and/or biogenesis of nuclear speckles. PMID: 21330300
- Through the bridging functions of Tat and AFF4, P-TEFb and ELL2 combine to form a bifunctional elongation complex that greatly activates HIV-1 transcription. PMID: 20471948
- AFF4 is required for super elongation complex stability and proper transcription by poised RNA polymerase II. PMID: 20159561
- MCEF has 21 exons & 7 nuclear localization sequence. 3 protein sequences, coded by 3 exons, mediate nuclear localization. Ectopic expression of MCEF repressed HIV-1 LTR-directed RNA polymerase II transcription, at the level of Tat-transactivation. PMID: 17389929
- Data describe the cloning and expression of MCEF, a member of the AF4 family of transcription factors involved in acute lymphoblastic leukemia. [MCEF] PMID: 12065898
|Involvement in disease
||CHOPS syndrome (CHOPS)
||Ubiquitously expressed. Strongly expressed in heart, placenta, skeletal muscle, pancreas and to a lower extent in brain.