Heterodimer formation of the myeloid zinc finger 1 SCAN domain and association with promyelocytic leukemia nuclear bodies.
Myeloid zinc finger 1 (MZF1) is a transcription factor that plays an important role in blood cell development. Previous reports indicate MZF1 is an essential factor whose abnormal expression results in cancer. However, the molecular mechanisms by which MZF1 functions in development and contributes to cancer progression remain unknown. MZF1 is a member of the SCAN domain family of zinc finger proteins (SCAN-ZFP) that form dimers via their highly conserved SCAN motif. To better understand the molecular mechanism of MZF1 function, we sought to characterize the cellular localization pattern of MZF1 in the context of SCAN dimerization. Here we provide evidence that MZF1 is a constituent of promyelocytic leukemia nuclear bodies (PML-NBs) and that the SCAN domain is necessary for association with these intranuclear structures. In addition, the SCAN-ZFP member ZNF24 was identified as a novel heterodimeric partner of MZF1 that also associates with PML-NBs in a unique ring-type pattern. Finally, we provide support that MZF1 protein may be modified by SUMOylation, which provides further support for localization of MZF1 protein complexes to PML-NBs. Altogether, these data suggest that MZF1 is recruited to PML-NBs and that the SCAN domain may play an integral role in regulating the localization of heterodimeric protein complexes to these intranuclear structures.
Noll
LeAnne
L
Department of Surgery, Children's Research Institute Medical College of Wisconsin, Milwaukee, WI 53226, United States.
Peterson
Francis C
FC
Hayes
Paulette L
PL
Volkman
Brian F
BF
Sander
Tara
T
D045744:Cell Line, Tumor; D022003:Cell Nucleus Structures / Q000737:chemistry*; D019281:Dimerization; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000032:analysis* / Q000737:chemistry* / Q000378:metabolism; D009687:Nuclear Proteins / Q000032:analysis; D017434:Protein Structure, Tertiary; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000032:analysis; D016335:Zinc Fingers
D051741:Kruppel-Like Transcription Factors; C085969:MZF1 protein, human; D009687:Nuclear Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; D014157:Transcription Factors