title: AF4 and AF4N protein complexes: recruitment of P-TEFb kinase, their interactome and potential functions.
abstract: AF4/AFF1 and AF5/AFF4 are the molecular backbone to assemble "super-elongation complexes" (SECs) that have two main functions: (1) control of transcriptional elongation by recruiting the positive transcription elongation factor b (P-TEFb = CyclinT1/CDK9) that is usually stored in inhibitory 7SK RNPs; (2) binding of different histone methyltransferases, like DOT1L, NSD1 and CARM1. This way, transcribed genes obtain specific histone signatures (e.g. H3K79me2/3, H3K36me2) to generate a transcriptional memory system. Here we addressed several questions: how is P-TEFb recruited into SEC, how is the AF4 interactome composed, and what is the function of the naturally occuring AF4N protein variant which exhibits only the first 360 amino acids of the AF4 full-length protein. Noteworthy, shorter protein variants are a specific feature of all AFF protein family members. Here, we demonstrate that full-length AF4 and AF4N are both catalyzing the transition of P-TEFb from 7SK RNP to their N-terminal domain. We have also mapped the protein-protein interaction network within both complexes. In addition, we have first evidence that the AF4N protein also recruits TFIIH and the tumor suppressor MEN1. This indicate that AF4N may have additional functions in transcriptional initiation and in MEN1-dependend transcriptional processes.
authors.affiliation: Institute of Pharmaceutical Biology, Goethe-University of Frankfurt Biocenter, Max-von-Laue-Str. 9, D-60438 Frankfurt/Main, Germany.
authors.forename: Bastian
authors.initials: B
authors.lastname: Scholz
authors.affiliation: Institute of Pharmaceutical Biology, Goethe-University of Frankfurt Biocenter, Max-von-Laue-Str. 9, D-60438 Frankfurt/Main, Germany.
authors.forename: Eric
authors.initials: E
authors.lastname: Kowarz
authors.affiliation: Institute of Pharmaceutical Biology, Goethe-University of Frankfurt Biocenter, Max-von-Laue-Str. 9, D-60438 Frankfurt/Main, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Rössler
authors.affiliation: Institute of Pharmaceutical Chemistry, Goethe-University of Frankfurt Biocenter, Max-von-Laue-Str. 9, D-60438 Frankfurt/Main, Germany.
authors.forename: Khalil
authors.initials: K
authors.lastname: Ahmad
authors.affiliation: Institute of Pharmaceutical Chemistry, Goethe-University of Frankfurt Biocenter, Max-von-Laue-Str. 9, D-60438 Frankfurt/Main, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Steinhilber
authors.affiliation: Institute of Pharmaceutical Biology, Goethe-University of Frankfurt Biocenter, Max-von-Laue-Str. 9, D-60438 Frankfurt/Main, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Marschalek
keywords: 7SK RNP; AF4/AF4N; P-TEFb; RNA polymerase II; elongation control