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c-myc proto-oncogene protein; transcription factor p64 (c-Myc, MYC)

Function: - role in the regulation of gene transcription - binds DNA both non-specifically & specifically - recognizes the core sequence 5'-CAC[GA]TG-3' - seems to activate the transcription of growth-related genes - c-myc is has been implicated in cell growth, proliferation, loss of differentiation & apoptosis - target genes include those for cyclin D2, CDK2, translation initiation factors eIF4 & eIF2 - c-myc is recruited to the p21WAF1/Cip1 promoter by MIZ-1; this blocks p21WAF1/Cip1 induction by p53 & other activators. - c-myc does not affect p53 binding but inhibits bound p53 from activating transcription. [5] - efficient DNA binding requires dimerization with another bHLH protein - binds DNA as a heterodimer with MAX; binds E-box - interacts with TAF1C & SPAG9 - interacts with PARP10 - interacts with JARID1A & JARID1B - phosphorylated by PRKDC Structure: - cellular homolog of the viral oncogene of avian myelocytomatosis retrovirus - contains 1 basic helix-loop-helix (bHLH) domain Compartment: nucleus Expression: - widely expressed in embryogenesis - adult tissues with high proliferation rates (epidermis, GI tract) Pathology: - overexpression of MYC is implicated in the etiology of a variety of hematopoietic tumors - chromosomal translocation t(8;12)(q24;q22) involving MYC with BTG1 may be a cause of B-cell chronic lymphocytic leukemia, Burkitt's lymphoma ? - overexpression of or deregulation of MYC has been found in a wide range of cancers including: a) breast cancer b) colon cancer c) cervical cancer d) small cell lung carcinoma e) osteosarcoma f) glioblastoma g) melanoma h) myeloid leukemia - overexpression of or deregulation of MYC may be associated with poor prognosis

Interactions

molecular events

Related

c-myc proto-oncogene C-Myc-binding protein; associate of Myc 1; AMY-1 (MYCBP, AMY1) myc/max complex

General

myc protein family PEST protein proto oncogene protein

Properties

SIZE: entity length = 439 aa MW = 49 kD COMPARTMENT: cell nucleus MOTIF: Thr phosphorylation site {T8} glutamine-rich region {33-37} MOTIF: glutamine residue (SEVERAL) Thr phosphorylation site {T58} Thr glycosylation site {T58} Ser phosphorylation site {S62} glycine-rich region {88-91} PEST region basic helix-loop-helix {354-407} MOTIF: DNA-binding motif SITE: 354-367 helix-loop-helix NAME: helix-loop-helix SITE: 368-407 FOR-BINDING-VIA: helix-loop-helix FOR-BINDING-OF: DNA motif FOR-BINDING-VIA: helix-loop-helix leucine zipper SITE: 413-434 FOR-BINDING-VIA: leucine zipper MISC-INFO: 1/2life 0.5 HOURS RECOGNITION-MOTIF :SEQUENCE CACGTG

References

  1. Dwarki VJ, Montminy M, Verma IM. Both the basic region and the 'leucine zipper' domain of the cyclic AMP response element binding (CREB) protein are essential for transcriptional activation. EMBO J. 1990 Jan;9(1):225-32. PMID: 2136830
  2. Rogers S et al, Amino acids common to rapidly degraded proteins: The PEST hypothesis Science 234:364 1986 (1/2life) PMID: 2876518
  3. Blackwell TK, Kretzner L, Blackwood EM, Eisenman RN, Weintraub H. Sequence-specific DNA binding by the c-Myc protein. Science. 1990 Nov 23;250(4984):1149-51. PMID: 2251503
  4. Pelengaris S, Khan M, Evan G. c-MYC: more than just a matter of life and death. Nat Rev Cancer. 2002 Oct;2(10):764-76. Review. PMID: 12360279
  5. Seoane J et al Myc suppression of the p21(Cip1) Cdk inhibitor influences the outcome of the p53 response to DNA damage. Nature. 2002 Oct 17;419(6908):729-34. Epub 2002 Oct 2. PMID: 12384701
  6. Herschman HR Extracellular signals, transcriptional responses and cellular specificity TIBS 14:455 1989 PMID: 2696174
  7. Atlas of genetics & cytogenetics in oncology & haematology http://atlasgeneticsoncology.org/genes/MYCID27.html Wikipedia; Note: Myc entry http://en.wikipedia.org/wiki/Myc
  8. UniProt :accession P01106

Component-of

molecular complex

Databases & Figures

OMIM 190080 MORBIDMAP 190080 UniProt P01106 PFAM correlations Entrez Gene 4609 Kegg hsa:4609 Damage-Related Inducers of Apoptosis