MRG15 activates the B-myb promoter through formation of a nuclear complex with the retinoblastoma protein and the novel protein PAM14
Open accessAbstract
The MORF4-Related Gene on chromosome 15 (MRG15) is a member of a novel family of genes originally identified in studies to reveal cell senescence-inducing factors. MRG15 contains several predicted protein motifs, including a nuclear localization signal, a helix-loop-helix region, a leucine zipper, and a chromodomain. These motifs are commonly associated with transcription factors, suggesting that MRG15 may likewise function as a transcriptional regulator. To examine the potential function(s) of MRG15, we sought to identify cellular factors associated with this MRG family member. In this regard, we have found that both the retinoblastoma tumor suppressor (Rb) and a novel nuclear protein PAM14 (Protein Associated with MRG, 14 kDa) specifically associate with MRG15. We have further demonstrated that these interactions require the helix-loop-helix and leucine zipper domains of MRG15. Interestingly we have found all three proteins present in a multiprotein complex, suggesting that at least some of their functions may be interdependent. Although the functions of PAM14 have yet to be elucidated, Rb has several well characterized activities, including repression of E2F-activated promoters such as that of B-myb. Significantly we have demonstrated that MRG15 blocks the Rb-induced repression of this promoter, leading to B-myb promoter activation. Collectively these results suggest that MRG15 regulates transcription through interactions with a cellular protein complex containing Rb and PAM14.
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The senescence response appears to result in a reorganization of chromatin, at least some aspects of which require pRB activity.
“Although specific mechanisms are as yet unknown, the senescence response appears to result in a reorganization of chromatin, at least some aspects of which require pRB activity (Jacobs et al., 1999; Leung et al., 2001; Bandyopadhyay et al., 2002; Itahana et al., 2003; Narita et al., 2003; Zhang et al., 2003, 2005).”
From Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors (2005) · cites this paper as Leung et al., 2001
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- Authors
- Leung, J. K., Berube, N., Venable, S., Ahmed, S., Timchenko, N., & Pereira-Smith, O. M.
- Affiliations
- Baylor College of Medicine (US)
- Corresponding author
- Leung, James K.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2001-10
- Volume
- 276
- Issue
- 42
- Pages
- 39171-39178
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2088149423
- Cited by
- 52
- References
- 23
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2018: 1 · 2016: 1 · 2015: 3 · 2014: 2 · 2013: 3 · 2012: 1
- FWCI
- 1.86
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r37ag005333-18)
- National Institute on Aging (R37-AG05333, T32AG000183)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- MRG15, retinoblastoma protein, transcriptional regulation, helix-loop-helix domain, leucine zipper domain, chromodomain, protein-protein interaction, protein complexes, cellular senescence, transcriptional repressor
- MeSH terms
- Amino Acid Sequence, Carrier Proteins, Cell Line, Cell Line, Transformed, Cell Nucleus, DNA-Binding Proteins, Glutathione Transferase, HeLa Cells, Humans, Luciferases, Luminescent Proteins, Microscopy, Fluorescence, Molecular Sequence Data, Mutation, Nuclear Proteins, Precipitin Tests, Promoter Regions, Genetic, Protein Binding, Transcription Factors, Transcription, Genetic, Tumor Cells, Cultured, Trans-Activators, Retinoblastoma Protein, Protein Structure, Tertiary, Cell Cycle Proteins, Intracellular Signaling Peptides and Proteins, Green Fluorescent Proteins
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