MYBL2 explained

Myb-related protein B is a protein that in humans is encoded by the MYBL2 gene.^[1]

Function

The protein encoded by this gene, a member of the MYB family of transcription factor genes, is a nuclear protein involved in cell cycle progression. The encoded protein is phosphorylated by cyclin A/cyclin-dependent kinase 2 during the S-phase of the cell cycle and possesses both activator and repressor activities. It has been shown to activate the cell division cycle 2, cyclin D1, and insulin-like growth factor-binding protein 5 genes. Transcript variants may exist for this gene, but their full-length natures have not been determined.^[2] MYBL2 is deregulated in various cancer types and can contribute to cancer progression.^{[3] [4]}

Interactions

MYBL2 has been shown to interact with:

• CDK9^[5]
• CREB-binding protein^[6]
• Cyclin A1^[7]
  • Cyclin-dependent kinase inhibitor 1C EP300^[8]
• PARP1^[9]
• Retinoblastoma-like protein 1^{[10] [11]}

Further reading

• Golay J, Cusmano G, Introna M . Independent regulation of c-myc, B-myb, and c-myb gene expression by inducers and inhibitors of proliferation in human B lymphocytes . Journal of Immunology . 149 . 1 . 300–8 . July 1992 . 10.4049/jimmunol.149.1.300 . 1376749 .
• Reiss K, Travali S, Calabretta B, Baserga R . Growth regulated expression of B-myb in fibroblasts and hematopoietic cells . Journal of Cellular Physiology . 148 . 3 . 338–43 . September 1991 . 1717494 . 10.1002/jcp.1041480303 . 30389377 .
• Golay J, Capucci A, Arsura M, Castellano M, Rizzo V, Introna M . Expression of c-myb and B-myb, but not A-myb, correlates with proliferation in human hematopoietic cells . Blood . 77 . 1 . 149–58 . January 1991 . 1984793 . 10.1182/blood.V77.1.149.149. free .
• Nomura N, Takahashi M, Matsui M, Ishii S, Date T, Sasamoto S, Ishizaki R . Isolation of human cDNA clones of myb-related genes, A-myb and B-myb . Nucleic Acids Research . 16 . 23 . 11075–89 . December 1988 . 3060855 . 338997 . 10.1093/nar/16.23.11075 .
• Lam EW, Bennett JD, Watson RJ . Cell-cycle regulation of human B-myb transcription . Gene . 160 . 2 . 277–81 . July 1995 . 7642110 . 10.1016/0378-1119(95)00184-8 .
• Takemoto Y, Tashiro S, Handa H, Ishii S . Multiple nuclear localization signals of the B-myb gene product . FEBS Letters . 350 . 1 . 55–60 . August 1994 . 8062924 . 10.1016/0014-5793(94)00733-0 . 45799740 . free .
• Zhou W, Takuwa N, Kumada M, Takuwa Y . E2F1, B-myb and selective members of cyclin/cdk subunits are targets for protein kinase C-mediated bimodal growth regulation in vascular endothelial cells . Biochemical and Biophysical Research Communications . 199 . 1 . 191–8 . February 1994 . 8123011 . 10.1006/bbrc.1994.1213 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . January 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Arsura M, Luchetti MM, Erba E, Golay J, Rambaldi A, Introna M . Dissociation between p93B-myb and p75c-myb expression during the proliferation and differentiation of human myeloid cell lines . Blood . 83 . 7 . 1778–90 . April 1994 . 8142646 . 10.1182/blood.V83.7.1778.1778. free .
• Nakagoshi H, Takemoto Y, Ishii S . Functional domains of the human B-myb gene product . The Journal of Biological Chemistry . 268 . 19 . 14161–7 . July 1993 . 10.1016/S0021-9258(19)85222-5 . 8314782 . free .
• Sala A, Kundu M, Casella I, Engelhard A, Calabretta B, Grasso L, Paggi MG, Giordano A, Watson RJ, Khalili K, Peschle C . 6 . Activation of human B-MYB by cyclins . Proceedings of the National Academy of Sciences of the United States of America . 94 . 2 . 532–6 . January 1997 . 9012818 . 19547 . 10.1073/pnas.94.2.532 . 1997PNAS...94..532S . free .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . October 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Saville MK, Watson RJ . The cell-cycle regulated transcription factor B-Myb is phosphorylated by cyclin A/Cdk2 at sites that enhance its transactivation properties . Oncogene . 17 . 21 . 2679–89 . November 1998 . 9840932 . 10.1038/sj.onc.1202503 . 23576308 .
• Bartsch O, Horstmann S, Toprak K, Klempnauer KH, Ferrari S . Identification of cyclin A/Cdk2 phosphorylation sites in B-Myb . European Journal of Biochemistry . 260 . 2 . 384–91 . March 1999 . 10095772 . 10.1046/j.1432-1327.1999.00191.x .
• Kim T, Jung H, Min S, Kim KT, Ha H . B-myb proto-oncogene products interact in vivo with each other via the carboxy-terminal conserved region . FEBS Letters . 460 . 2 . 363–8 . October 1999 . 10544265 . 10.1016/S0014-5793(99)01375-7 . 36560086 . free .
• Johnson TK, Schweppe RE, Septer J, Lewis RE . Phosphorylation of B-Myb regulates its transactivation potential and DNA binding . The Journal of Biological Chemistry . 274 . 51 . 36741–9 . December 1999 . 10593981 . 10.1074/jbc.274.51.36741 . free .
• Horstmann S, Ferrari S, Klempnauer KH . Regulation of B-Myb activity by cyclin D1 . Oncogene . 19 . 2 . 298–306 . January 2000 . 10645009 . 10.1038/sj.onc.1203302 . 8417008 . free .
• De Falco G, Bagella L, Claudio PP, De Luca A, Fu Y, Calabretta B, Sala A, Giordano A . 6 . Physical interaction between CDK9 and B-Myb results in suppression of B-Myb gene autoregulation . Oncogene . 19 . 3 . 373–9 . January 2000 . 10656684 . 10.1038/sj.onc.1203305 . free .
• Cervellera MN, Sala A . Poly(ADP-ribose) polymerase is a B-MYB coactivator . The Journal of Biological Chemistry . 275 . 14 . 10692–6 . April 2000 . 10744766 . 10.1074/jbc.275.14.10692 . free .

Notes and References

1. Noben-Trauth K, Copeland NG, Gilbert DJ, Jenkins NA, Sonoda G, Testa JR, Klempnauer KH . Mybl2 (Bmyb) maps to mouse chromosome 2 and human chromosome 20q 13.1 . Genomics . 35 . 3 . 610–2 . August 1996 . 8812502 . 10.1006/geno.1996.0408 .
2. Web site: Entrez Gene: MYBL2 v-myb myeloblastosis viral oncogene homolog (avian)-like 2.
3. Musa J, Aynaud MM, Mirabeau O, Delattre O, Grünewald TG . MYBL2 (B-Myb): a central regulator of cell proliferation, cell survival and differentiation involved in tumorigenesis . Cell Death & Disease . 8 . 6 . e2895 . June 2017 . 28640249 . 5520903 . 10.1038/cddis.2017.244 .
4. Musa J, Cidre-Aranaz F, Aynaud MM, Orth MF, Knott MM, Mirabeau O, Mazor G, Varon M, Hölting TL, Grossetête S, Gartlgruber M, Surdez D, Gerke JS, Ohmura S, Marchetto A, Dallmayer M, Baldauf MC, Stein S, Sannino G, Li J, Romero-Pérez L, Westermann F, Hartmann W, Dirksen U, Gymrek M, Anderson ND, Shlien A, Rotblat B, Kirchner T, Delattre O, Grünewald TG . 6 . Cooperation of cancer drivers with regulatory germline variants shapes clinical outcomes . Nature Communications . 10 . 1 . 4128 . September 2019 . 31511524 . 6739408 . 10.1038/s41467-019-12071-2 . 2019NatCo..10.4128M .
5. De Falco G, Bagella L, Claudio PP, De Luca A, Fu Y, Calabretta B, Sala A, Giordano A . 6 . Physical interaction between CDK9 and B-Myb results in suppression of B-Myb gene autoregulation . Oncogene . 19 . 3 . 373–9 . January 2000 . 10656684 . 10.1038/sj.onc.1203305 . free .
6. Bessa M, Saville MK, Watson RJ . Inhibition of cyclin A/Cdk2 phosphorylation impairs B-Myb transactivation function without affecting interactions with DNA or the CBP coactivator . Oncogene . 20 . 26 . 3376–86 . June 2001 . 11423988 . 10.1038/sj.onc.1204439 . free .
7. Müller-Tidow C, Wang W, Idos GE, Diederichs S, Yang R, Readhead C, Berdel WE, Serve H, Saville M, Watson R, Koeffler HP . 6 . Cyclin A1 directly interacts with B-myb and cyclin A1/cdk2 phosphorylate B-myb at functionally important serine and threonine residues: tissue-specific regulation of B-myb function . Blood . 97 . 7 . 2091–7 . April 2001 . 11264176 . 10.1182/blood.V97.7.2091 . free .
8. Johnson LR, Johnson TK, Desler M, Luster TA, Nowling T, Lewis RE, Rizzino A . Effects of B-Myb on gene transcription: phosphorylation-dependent activity and acetylation by p300 . The Journal of Biological Chemistry . 277 . 6 . 4088–97 . February 2002 . 11733503 . 10.1074/jbc.M105112200 . free .
9. Cervellera MN, Sala A . Poly(ADP-ribose) polymerase is a B-MYB coactivator . The Journal of Biological Chemistry . 275 . 14 . 10692–6 . April 2000 . 10744766 . 10.1074/jbc.275.14.10692 . free .
10. Joaquin M, Watson RJ . The cell cycle-regulated B-Myb transcription factor overcomes cyclin-dependent kinase inhibitory activity of p57(KIP2) by interacting with its cyclin-binding domain . The Journal of Biological Chemistry . 278 . 45 . 44255–64 . November 2003 . 12947099 . 10.1074/jbc.M308953200 . free .
11. Joaquin M, Bessa M, Saville MK, Watson RJ . B-Myb overcomes a p107-mediated cell proliferation block by interacting with an N-terminal domain of p107 . Oncogene . 21 . 52 . 7923–32 . November 2002 . 12439743 . 10.1038/sj.onc.1206001 . 21761703 .