How the sequestration of a protein interferes with its mechanism of action: example of a new family of proteins characterized by a particular cysteine-rich carboxy-terminal domain involved in gene expression regulation.
We describe here a new family of proteins characterized by a particular cysteine-rich carboxy-terminal domain and involved in gene expression regulation. This family presently includes three members: I-mfa (inhibitor of MyoD family), HIC p40 and HIC p32 (human I-mfa domain-containing protein). I-mfa, by interacting with MyoD family members, represses both transcriptional activation and myogenesis mediated by these factors. HIC two isoforms, HIC p40 and HIC p32, are involved in the positive regulation of Tax-mediated HTLV-I (human T-cell leukemia virus type 1) promoter activation and in the negative regulation of Tat-mediated HIV-1 (human immunodeficiency virus type 1) promoter transcription. The common carboxy-terminal region of HIC p40 and HIC p32, which is clearly involved in these regulations, shares 77% homology with the carboxy-terminal domain of I-mfa. This suggests that I-mfa, HIC p40 and HIC p32 are part of a new family of proteins involved in gene expression regulation and characterized by a specific cysteine-rich carboxy-terminal domain. Moreover, the three proteins present different subcellular localizations: I-mfa and HIC p32 are mainly cytoplasmic while HIC p40 is mainly nucleolar. The specific localization of each member of this new family will be discussed, possibly explaining how they work. Effectively, a mechanism of protein sequestration in a particular compartment, cytoplasm or nucleolus, could be involved in their function, as it is the case for many other proteins. This relationship between sequestration and function regulation will be exemplified for several cellular factors.
Thébault
S
S
Gladstone Institute of Virology and Immunology, PO Box 419100, San Francisco, CA 94141-9100, USA. sthebault@gladstone.ucsf.edu
Mesnard
J M
JM
D000595:Amino Acid Sequence; D002451:Cell Compartmentation; D002467:Cell Nucleus / Q000378:metabolism; D003545:Cysteine / Q000737:chemistry; D003593:Cytoplasm / Q000378:metabolism; D005786:Gene Expression Regulation; D016356:Gene Products, tax / Q000235:genetics; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D018006:Myogenic Regulatory Factors / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D016356:Gene Products, tax; D018006:Myogenic Regulatory Factors; D016328:NF-kappa B; D011506:Proteins; D016159:Tumor Suppressor Protein p53; C101295:MDFI protein, human; D020928:Mitogen-Activated Protein Kinases; D003545:Cysteine