High impact information on POLDIP2

• Colabeling with cell-specific markers revealed that macrophages expressed the alpha and gamma isoforms, synovial fibroblasts the beta and gamma isoforms, and granulocytes the delta isoform, whereas T lymphocytes were rarely positive for any p38 MAPK isoform [1].
• By immunohistochemistry, the expression of all p38 MAPK isoforms was localized to the synovial lining layer as well as to blood vessels [1].
• This phosphorylation pattern was confirmed in immunoprecipitation studies in which activated p38 MAPK from synovial tissue extracts was identified as p38 MAPKalpha and -gamma but not p38 MAPKbeta or -delta [1].
• PDIP38 was also found to interact with proliferating cell nuclear antigen, which suggested that it might play a role in vivo in the processes of DNA replication and DNA repair in the nucleus [2].
• These studies show that PDIP38 is a novel mitochondrial protein and is localized mainly to the mitochondria [2].

Biological context of POLDIP2

• Although the localization of PDIP38 to the mitochondria suggests that it serves functions within the mitochondria, we cannot eliminate the possibility that it may be involved in pol delta-mediated DNA replication or DNA repair under certain conditions such as viral infection [2].
• PDIP38 was initially identified as a binding protein to nuclear DNA polymerase delta [3].

Anatomical context of POLDIP2

• PDIP38 is almost exclusively recovered from the mitochondrial fraction of human HeLa cells [3].

Associations of POLDIP2 with chemical compounds

• Lastly, the actions of bryostatin 1 were mimicked by a pharmacologic inhibitor of the MEK1/MAP kinase pathway (PD98059), but not by SB203580, an inhibitor of p 38 MAP kinase [4].
• On the other hand, only the latter is crosslinked to PDIP38 when mitochondria are treated with a crosslinker, formaldehyde [3].

Physical interactions of POLDIP2

• TFAM and mitochondrial single-stranded DNA binding protein (mtSSB) are co-immunoprecipitated with PDIP38 by anti-PDIP38 antibodies [3].

Enzymatic interactions of POLDIP2

• PDIP38 is completely cleaved when TritonX-100-solubilized mitochondria are treated with proteinase K, but not when mitoplasts devoid of outer membranes are treated, indicating that PDIP38 is located in the mitochondrial matrix [3].

Other interactions of POLDIP2

• The PCNA-PDIP38 interaction was also demonstrated by PCNA overlay experiments [5].
• During an attempt to search for proteins associated with the TFAM-containing complex by a proteomic method, we found one protein that has not been considered to be mitochondrial: PDIP38 [3].

Analytical, diagnostic and therapeutic context of POLDIP2

• The expression and activation of the alpha, beta, gamma, and delta isoforms of p38 MAPK were examined by immunoblotting, immunoprecipitation, and immunohistochemistry [1].

References